VAMOROLONE SOLID ORAL DOSAGE FORMS JOINT RESEARCH AGREEMENT [0001] The subject matter disclosed in this application was developed, and the claimed invention was made by, or on behalf of, Catalyst Pharmaceuticals, Inc. and Santhera Pharmaceuticals (Schweiz) AG, parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention. The claimed invention was made as a result of activities undertaken within the scope of the joint research agreement. BACKGROUND [0002] Vamorolone, marketed under the trade name AGAMREE®, is a synthetic corticosteroid indicated for the treatment of Duchenne muscular dystrophy. Vamorolone is currently administered as an oral suspension to facilitate ready mg/kg dosing. There remains a need to develop solid oral dosage forms of vamorolone, e.g., tablets or capsules, which are easier to store and administer. BRIEF SUMMARY [0003] In some aspects, the present disclosure provides a pharmaceutical composition comprising: a) an amorphous solid dispersion comprising amorphous vamorolone and a pharmaceutically acceptable polymer; and b) one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is a solid oral dosage form. [0004] In some aspects, the amorphous solid dispersion comprises from about 15 wt% to about 95 wt% vamorolone and about 5 wt% to about 85 wt% of the polymer. [0005] In some aspects, the amorphous solid dispersion comprises from about 20 wt% to about 50 wt% vamorolone and about 50 wt% to about 80 wt% of the polymer. [0006] In some aspects, the pharmaceutically acceptable polymer is selected from the group consisting of hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone, copovidone, polyvinyl caprolactam-polyvinyl
acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid), and combinations thereof. [0007] In some aspects, the pharmaceutically acceptable polymer is selected from the group consisting of hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, cellulose acetate phthalate, methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), povidone, copovidone, and polyvinyl caprolactam- polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®). [0008] In some aspects, the amorphous solid dispersion further comprises a plasticizer, a surfactant, a filler, or a combination of any of the foregoing. [0009] In some aspects, the amorphous solid dispersion further comprises a plasticizer. [0010] In some aspects, the plasticizer comprises a citrate ester, a fatty acid ester, a phthalate ester, poly(ethylene glycol), poly(propylene glycol), tocopherol polyethylene glycol succinate, dibutyl sebacate, triacetin, a polysorbate, a sugar alcohol, or a combination of any of the foregoing. [0011] In some aspects, the plasticizer comprises poly(ethylene glycol). [0012] In some aspects, the amorphous solid dispersion further comprises a surfactant. [0013] In some aspects, the surfactant comprises sodium lauryl sulfate, a poloxamer, a polysorbate, tocopherol polyethylene glycol succinate, poly(ethylene glycol), a fatty acid triglyceride, or a combination of any of the foregoing. [0014] In some aspects, the surfactant comprises a poloxamer. [0015] In some aspects, the filler comprises microcrystalline cellulose, silicified microcrystalline cellulose, carboxymethylcellulose sodium, methylcellulose, hydroxyethylmethyl cellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, povidone, copovidone, lactose monohydrate, lactose anhydrous, mannitol, sucrose, dextrates (EMDEX® or CAMDEX®), maltodextrin, polydextrose, starch, pregelatinized starch, hydroxypropyl starch, carbomer, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate and maltodextrin, polycarbophil, or a combination of any of the foregoing.
[0016] In some aspects, the amorphous solid dispersion is provided as a plurality of granules or pellets. [0017] In some aspects, the pharmaceutical composition comprises from about 20 wt% to about 95 wt% of the amorphous solid dispersion. [0018] In some aspects, the pharmaceutical composition comprises from about 10 wt% to about 50 wt% of the amorphous solid dispersion. [0019] In some aspects, the amorphous solid dispersion is prepared by hot melt extrusion, twin screw melt granulation, high shear melt granulation, or spray drying. [0020] In some aspects, the solid oral dosage form is a tablet or capsule. [0021] In some aspects, the one or more pharmaceutically acceptable excipients comprises one or more diluents, one or more disintegrants, one or more lubricants, one or more flow enhancers, or a combination of any of the foregoing. [0022] In some aspects, the one or more diluents comprises microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, sucrose, starch, pregelatinized starch, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate, maltodextrin, or a combination of any of the foregoing. [0023] In some aspects, the one or more diluents comprises microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, or a combination of any of the foregoing. [0024] In some aspects, the pharmaceutical composition comprises from about 5 wt% to about 85 wt% of the one or more diluents. [0025] In some aspects, the one or more disintegrants comprises croscarmellose sodium, carmellose sodium, sodium starch glycolate, carboxymethylcellulose sodium, carboxymethylcellulose calcium, crospovidone, starch, microcrystalline cellulose, low- substituted hydroxypropyl cellulose, or a combination of any of the foregoing. [0026] In some aspects, the one or more disintegrants comprises croscarmellose sodium, sodium starch glycolate, crospovidone, or a combination of any of the foregoing. [0027] In some aspects, the pharmaceutical composition comprises from about 0.25 wt% to about 10 wt% of the one or more disintegrants. [0028] In some aspects, the one or more lubricants comprises magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing.
[0029] In some aspects, the one or more lubricants comprises magnesium stearate or sodium stearyl fumarate. [0030] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 5 wt% of the one or more lubricants. [0031] In some aspects, the one or more flow enhancers comprises magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing. [0032] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 5 wt% of the one or more flow enhancers. [0033] In some aspects, the solid oral dosage form is a tablet, optionally wherein the tablet is coated with one or more film coating materials. [0034] In some aspects, the one or more film coating materials is not optional and is hydroxypropyl methylcellulose, poly(vinyl acetate), hydroxypropyl cellulose, polyethylene glycol, or a combination of any of the foregoing. [0035] In some aspects, the pharmaceutical composition comprises from about 1 wt% to about 10 wt% of the one or more film coating materials. [0036] In some aspects, the solid oral dosage form is a powder for suspension. [0037] In some aspects, the one or more pharmaceutically acceptable excipients comprises one or more suspending agents, one or more buffering agents, one or more wetting agents, one or more preservatives, one or more flavoring agents, one or more flow enhancers, or a combination of any of the foregoing. [0038] In some aspects, the one or more suspending agents comprises hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing. [0039] In some aspects, the pharmaceutical composition comprises from about 5 wt% to about 80 wt% of the one or more suspending agents. [0040] In some aspects, the one or more buffering agents comprises a citrate buffer, a phosphate buffer, a carbonate buffer, or a combination of any of the foregoing. [0041] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 5 wt% of the one or more buffering agents. [0042] In some aspects, the one or more wetting agents comprises sodium lauryl sulfate, a poloxamer, a polysorbate, or a combination of any of the foregoing.
[0043] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 10 wt% of the one or more wetting agents. [0044] In some aspects, the one or more preservatives comprises methyl paraben, propyl paraben, sodium benzoate, citric acid, ascorbic acid, or a combination of any of the foregoing. [0045] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 5 wt% of the one or more preservatives. [0046] In some aspects, the one or more flavoring agents comprises sucrose, aspartame, an artificial flavor, a natural flavor, or a combination of any of the foregoing. [0047] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 5 wt% of the one or more flavoring agents. [0048] In some aspects, the one or more flow enhancers comprises colloidal silicon dioxide, talc, glycerol monostearate, magnesium monostearate, or a combination thereof. [0049] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 5 wt% of the one or more flow enhancers. [0050] In some aspects, the present disclosure provides a process for preparing a pharmaceutical composition disclosed herein, comprising: a) admixing vamorolone, a polymer, and optionally one or more of a plasticizer, a surfactant, or a filler, to form a mixture; b) extruding the mixture to form an amorphous solid dispersion; c) pelletizing or milling the amorphous solid dispersion; and d) admixing the amorphous solid dispersion with one or more pharmaceutically acceptable excipients. [0051] In some aspects, the present disclosure provides a process for preparing a pharmaceutical composition disclosed herein, comprising: a) admixing vamorolone, a polymer, and an organic solvent to form a mixture; b) spray drying the mixture to form an amorphous solid dispersion; and c) admixing the amorphous solid dispersion with one or more pharmaceutically acceptable excipients. [0052] In some aspects, the present disclosure provides a pharmaceutical composition comprising: a) a plurality of coated particles, wherein each coated particle comprises: i) an inert core;
ii) a first drug layer coated over the inert core, the first drug layer comprising amorphous vamorolone and a first polymer; and iii) a first encapsulation layer coated over the first drug layer, the first encapsulation layer comprising a second polymer; and b) optionally one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is a solid oral dosage form. [0053] In some aspects, the inert core is a microcrystalline cellulose sphere, a sugar sphere, a silica sphere, dicalcium phosphate anhydrous, magnesium alumino-metasilicate, microcrystalline cellulose, or a combination of any of the foregoing. [0054] In some aspects, the inert core comprises from about 5 wt% to about 90 wt% of a total mass of the coated particle [0055] In some aspects, the first polymer comprises hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing. [0056] In some aspects, the first drug layer is present comprises from about 30 wt% to about 80 wt% of the total mass of the coated particle. [0057] In some aspects, the second polymer comprises hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing. [0058] In some aspects, the first polymer and the second polymer are the same. [0059] In some aspects, the first encapsulation layer comprises from about 30 wt% to about 80 wt % of the total mass of the coated particle. [0060] In some aspects, the pharmaceutical composition comprises from about 20 wt% to about 95 wt% of the coated particles. [0061] In some aspects, the particles are prepared by fluid bed drug layering. [0062] In some aspects, the solid oral dosage form is a tablet or capsule. [0063] In some aspects, the one or more pharmaceutically acceptable excipients comprises one or more diluents, one or more disintegrants, one or more lubricants, one or more flow enhancers, or a combination of any of the foregoing.
[0064] In some aspects, the one or more diluents comprises microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, sucrose, starch, pregelatinized starch, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate and maltodextrin, or a combination of any of the foregoing. [0065] In some aspects, the pharmaceutical composition comprises from about 5 wt% to about 85 wt% of the one or more diluents. [0066] In some aspects, the one or more disintegrants comprises croscarmellose sodium, carmellose sodium, sodium starch glycolate, carboxymethylcellulose sodium, carboxymethylcellulose calcium, crospovidone, starch, microcrystalline cellulose, low- substituted hydroxypropyl cellulose, or a combination of any of the foregoing. [0067] In some aspects, the pharmaceutical composition comprises from about 0.25 wt% to about 10 wt% of the one or more disintegrants. [0068] In some aspects, the one or more lubricants comprises magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing. [0069] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 5 wt% of the one or more lubricants. [0070] In some aspects, the one or more flow enhancers comprises magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination thereof. [0071] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 5 wt% of the one or more flow enhancers. [0072] In some aspects, the solid oral dosage form is a tablet, wherein the tablet is coated with one or more film coating materials. [0073] In some aspects, the one or more film coating materials comprises hydroxypropyl methylcellulose, poly(vinyl acetate), hydroxypropyl cellulose, polyethylene glycol, or a combination thereof. [0074] In some aspects, the pharmaceutical composition comprises from about 1 wt% to about 10 wt% of the one or more film coating materials. [0075] In some aspects, the solid oral dosage form is a powder for suspension. [0076] In some aspects, the one or more pharmaceutically acceptable excipients comprises one or more suspending agents, one or more buffering agents, one or more
wetting agents, one or more preservatives, one or more flavoring agents, one or more flow enhancers, one or more antifoaming agents, or a combination of any of the foregoing. [0077] In some aspects, the one or more suspending agents comprises hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing. [0078] In some aspects, the pharmaceutical composition comprises from about 5 wt% to about 80 wt% of the one or more suspending agents. [0079] In some aspects, the one or more buffering agents comprises a citrate buffer, a phosphate buffer, a carbonate buffer, or a combination of any of the foregoing. [0080] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 5 wt% of the one or more buffering agents. [0081] In some aspects, the one or more wetting agents comprises sodium lauryl sulfate, a poloxamer, a polysorbate, or a combination of any of the foregoing. [0082] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 10 wt% of the one or more wetting agents. [0083] In some aspects, the one or more preservatives comprises methyl paraben, propyl paraben, sodium benzoate, citric acid, ascorbic acid, or a combination of any of the foregoing. [0084] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 5 wt% of the one or more preservatives. [0085] In some aspects, the one or more flavoring agents comprises sucrose, aspartame, an artificial flavor, a natural flavor, or a combination of any of the foregoing. [0086] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 5 wt% of the one or more flavoring agents. [0087] In some aspects, the one or more flow enhancers comprises colloidal silicon dioxide, talc, glycerol monostearate, magnesium monostearate, or a combination of any of the foregoing. [0088] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 5 wt% of the one or more flow enhancers.
[0089] In some aspects, the one or more antifoaming agents comprises simethicone (polydimethylsiloxane-silicon dioxide), an alcohol, an insoluble oil, a stearate, a polydimethylsiloxane, an ether, a glycol, or a combination of any of the foregoing. [0090] In some aspects, the pharmaceutical composition comprises from about 0.01 wt% to about 10 wt% of the one or more antifoaming agents. [0091] In some aspects, the present disclosure provides a pharmaceutical composition comprising: a) a plurality of coated particles, wherein each coated particle comprises: i) a core comprising amorphous vamorolone and a first polymer; and ii) a first encapsulation layer coated over the core, the first encapsulation layer comprising a second polymer; and b) optionally one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is a solid oral dosage form. [0092] In some aspects, the present disclosure provides a pharmaceutical composition comprising crystalline vamorolone and one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is a solid oral dosage form. [0093] In some aspects, the crystalline vamorolone is vamorolone crystalline Form I. [0094] In some aspects, the one or more pharmaceutically acceptable excipients comprises one or more diluents, one or more binders, one or more disintegrants, one or more lubricants, or a combination of any of the foregoing. [0095] In some aspects, the one or more diluents comprises microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, lactose, starch, dicalcium phosphate dihydrate, or a combination of any of the foregoing. [0096] In some aspects, the pharmaceutical composition comprises from about 20 wt% to about 85 wt% of the one or more diluents. [0097] In some aspects, the one or more binders comprises povidone, copovidone, hydroxpropylmethyl cellulose, hydroxypropyl cellulose, or a combination of any of the foregoing. [0098] In some aspects, the pharmaceutical composition comprises from about 0.5 wt% to about 10 wt% of the one or more binders. [0099] In some aspects, the one or more disintegrants comprises crosscarmellose sodium, sodium starch glycolate (EXPLOTAB®), cross povidone, or a combination of any of the foregoing.
[0100] In some aspects, the pharmaceutical composition comprises from about 0.5 wt% to about 7 wt% of the one or more disintegrants. [0101] In some aspects, the one or more lubricants comprises magnesium stearate, steric acid, glyceryl dibehenate, sodium steryl fumarate, or a combination of any of the foregoing. [0102] In some aspects, the pharmaceutical composition comprises from about 0.1 wt% to about 4 wt% of the one or more lubricants. [0103] In some aspects, the pharmaceutical composition further comprises an amorphous solid dispersion comprising amorphous vamorolone and a pharmaceutically acceptable polymer. [0104] In some aspects, the amorphous solid dispersion comprises from about 15 wt% to about 95 wt% vamorolone and about 5 wt% to about 85 wt% of the polymer. [0105] In some aspects, the pharmaceutically acceptable polymer is selected from the group consisting of hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone, copovidone, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid), and combinations thereof. [0106] In some aspects, the amorphous solid dispersion further comprises a plasticizer, a surfactant, a filler, or a combination of any of the foregoing. [0107] In some aspects, the plasticizer comprises a citrate ester, a fatty acid ester, a phthalate ester, poly(ethylene glycol), poly(propylene glycol), tocopherol polyethylene glycol succinate, dibutyl sebacate, triacetin, a polysorbate, a sugar alcohol, or a combination of any of the foregoing. [0108] In some aspects, the amorphous solid dispersion further comprises a surfactant. [0109] In some aspects, the surfactant comprises sodium lauryl sulfate, a poloxamer, a polysorbate, tocopherol polyethylene glycol succinate, poly(ethylene glycol), a fatty acid triglyceride, or a combination of any of the foregoing.
[0110] In some aspects, the filler comprises microcrystalline cellulose, silicified microcrystalline cellulose, carboxymethylcellulose sodium, methylcellulose, hydroxyethylmethyl cellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, povidone, copovidone, lactose monohydrate, lactose anhydrous, mannitol, sucrose, dextrates (EMDEX® or CAMDEX®), maltodextrin, polydextrose, starch, pregelatinized starch, hydroxypropyl starch, carbomer, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate and maltodextrin, polycarbophil, or a combination of any of the foregoing. [0111] In some aspects, the amorphous solid dispersion is provided as a plurality of granules or pellets. [0112] In some aspects, the pharmaceutical composition comprises from about 0.5 wt% to about 10 wt% of the amorphous solid dispersion. [0113] In some aspects, the amorphous solid dispersion is prepared by hot melt extrusion, twin screw melt granulation, high shear melt granulation, or spray drying. [0114] In some aspects, the pharmaceutical composition is prepared by direct blending. [0115] In some aspects, the present disclosure provides a process for preparing a pharmaceutical composition disclosed herein, comprising admixing crystalline vamorolone with one or more pharmaceutically acceptable excipients. [0116] In some aspects, the pharmaceutical composition has a total mass ranging from about 50 mg to about 800 mg. [0117] In some aspects, the total mass of the pharmaceutical composition is about 150 mg. [0118] In some aspects, the total mass of the pharmaceutical composition is about 300 mg. [0119] In some aspects, the pharmaceutical composition has a friability of less than 1.0% as measured using USP<1216>. [0120] In some aspects, the pharmaceutical composition has a disintegration time of less than 10 minutes. [0121] In some aspects, the pharmaceutical composition has a hardness of from about 5 kp to about 20 kp.
[0122] In some aspects, when the pharmaceutical composition is administered to a subject with food, the composition provides a vamorolone Tmax of from about 0.5 hours to about 5 hours. [0123] In some aspects, when the pharmaceutical composition is administered to a subject with food, the composition provides a vamorolone median Tmax of about 2 hours. [0124] In some aspects, when the pharmaceutical composition is administered to a subject with food, the composition provides a vamorolone AUC24 of from about 2,600 ng∙h/mL to about 4,350 ng∙h/mL. [0125] In some aspects, when the pharmaceutical composition is administered to a subject with food, the composition provides a vamorolone Cmax of from about 650 ng/mL to about 1,200 mg/mL. [0126] In some aspects, the present disclosure provides a method of treating muscular dystrophy in a subject in need thereof, comprising orally administering a pharmaceutical composition disclosed herein. [0127] In some aspects, the pharmaceutical composition is administered once, twice, or three times per day. [0128] In some aspects, the pharmaceutical composition is administered with food. [0129] In some aspects, the pharmaceutical composition is administered without food. [0130] In some aspects, the muscular dystrophy is Duchenne muscular dystrophy, Becker muscular dystrophy, limb girdle muscular dystrophy, congenital muscular dystrophy, facioscapulohumeral muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, distal muscular dystrophy, or Emery-Dreifuss muscular dystrophy. [0131] In some aspects, the muscular dystrophy is Duchenne muscular dystrophy. [0132] In some aspects, a total daily dose of vamorolone of from about 2 mg/kg to about 6 mg/kg is administered to the subject. [0133] In some aspects, the total daily dose of vamorolone is about 6 mg/kg. [0134] In some aspects, the subject is at least two years of age. [0135] In some aspects, the pharmaceutical composition comprises from about 5 mg to about 500 mg amorphous vamorolone. [0136] In some aspects, the pharmaceutical composition comprises from about 30 mg to about 300 mg amorphous vamorolone. [0137] In some aspects, the pharmaceutical composition comprises from about 100 mg to about 300 mg amorphous vamorolone.
[0138] Additional embodiments and advantages of the disclosure will be set forth, in part, in the description that follows, and will flow from the description, or can be learned by practice of the disclosure. [0139] It is to be understood that both the foregoing summary and the following detailed description are exemplary and explanatory only, and do not restrict the scope of the claims. BRIEF DESCRIPTION OF THE FIGURES [0140] FIG.1 is a flow chart depicting a procedure for preparing solid oral dosage forms using high shear granulation, as described in Example 9. [0141] FIG.2 is a flow chart depicting a procedure for preparing solid oral dosage forms using top spray granulation, as described in Example 10. [0142] FIG.3 is a flow chart depicting a procedure for preparing solid oral dosage forms using high shear granulation and a lipid binder, as described in Example 11. [0143] FIG.4 is a flow chart depicting a procedure for preparing solid oral dosage forms using high shear granulation and a lipid carrier, as described in Example 12. [0144] FIG.5 is a flow chart depicting a procedure for preparing solid oral dosage forms using high shear granulation and a cyclodextrin, as described in Example 13. [0145] FIG.6 is a flow chart depicting a procedure for preparing solid oral dosage forms using drug layering, as described in Example 14. [0146] FIG.7 is a flow chart depicting a procedure for preparing solid oral dosage forms using direct blending, as described in Example 15. [0147] FIG.8 is a flow chart depicting a procedure for preparing solid oral dosage forms using wet granulation, as described in Example 16. [0148] FIG.9 is a phase diagram depicting the solubility of vamorolone in KOLLIDON® VA64 and poloxamer P188. [0149] FIG.10 is a phase diagram depicting the solubility of vamorolone in SOLUPLUS®. [0150] FIG.11 is a phase diagram depicting the solubility of vamorolone in PVA 4-88 and poloxamer P188. [0151] FIG.12 is a phase diagram depicting the solubility of vamorolone in HPMCAS MMP.
[0152] FIG.13 is a line graph depicting the release of vamorolone over time from a vamorolone oral suspension or loose hot melt extrudate (HME) granules comprising 30% vamorolone and 5% or 10% LABRASOL®. [0153] FIG.14 is a line graph depicting release of vamorolone over time from a vamorolone oral suspension or loose HME granules comprising 10%, 20%, or 30% vamorolone, PVP K30 and 5% PEG4000. [0154] FIG.15 is a line graph depicting release of vamorolone over time from a vamorolone oral suspension or loose HME granules comprising 10% vamorolone in i) KOLLIDON® VA64 and 5% poloxamer P188; ii) SOLUPLUS® and 5% poloxamer P188; iii) HPMCAS MMP and 5% poloxamer P188; or iv) PVP K30 and 5% PEG4000. [0155] FIG.16 is a line graph depicting release of vamorolone over time from a vamorolone oral suspension or HME granules in capsules comprising 10% vamorolone in i) KOLLIDON® VA64 and 5% poloxamer P188; ii) SOLUPLUS® and 5% poloxamer P188; or iii) HPMCAS MMP. [0156] FIG.17 is a line graph depicting release of vamorolone over time from a vamorolone oral suspension or HME granules in capsules comprising 10%, 20%, or 30% vamorolone in KOLLIDON® VA64 and 5% poloxamer P188. [0157] FIG.18 is a line graph depicting release of vamorolone over time from a vamorolone oral suspension or a formulation comprising HME granules (comprising different polymers) and additional components filled in capsules as described in Example 6a. [0158] FIG.19 is a line graph depicting release of vamorolone over time from a vamorolone oral suspension or a formulation comprising HME granules (comprising different loadings of vamolorone) and additional components filled in capsules as described in Example 6a. [0159] FIG.20 is a line graph depicting release of vamorolone over time from a vamorolone oral suspension or tablets or granules comprising 20%, 30%, or 40% vamorolone in PVP K30 and 5% PEG4000. [0160] FIG.21 is a line graph depicting release of vamorolone over time from a vamorolone oral suspension or tablets comprising 30% vamorolone in PVP K30 having different hardnesses.
[0161] FIG.22 is a line graph depicting release of vamorolone over time from a vamorolone oral suspension or tablets comprising 30% vamorolone in PVP K30 having different tablet weights. [0162] FIG.23 is a line graph depicting release of vamorolone over time from a vamorolone oral suspension or 150 mg tablets comprising 30% vamorolone in PVP K30 or KOLLIDON® VA64. [0163] FIG.24 is a line graph depicting release of vamorolone over time from a vamorolone oral suspension or 150 mg (30 mg vamorolone) or 750 mg (150 mg vamorolone) tablets comprising spray dried dispersions comprising 50% vamorolone and 50% cellulose acetate phthalate (CAP). [0164] FIG.25 is a line graph depicting the compressibility of tablets having Formulations F134-F137 as prepared as described in Example 6d. [0165] FIG.26 is a line graph depicting the compactibility of tablets having Formulations F134-F137 as prepared as described in Example 6d. [0166] FIG.27 is a line graph depicting the tabletability of tablets having Formulations F134-F137 as prepared as described in Example 6d. [0167] FIG.28 is a line graph depicting the disintegration time of tablets having Formulations F134-F137 as prepared as described in Example 6d. [0168] FIG.29 is a line graph depicting the compressibility of tablets having Formulations F138-F140 (containing 30 mg vamolorone) as prepared as described in Example 6d. [0169] FIG.30 is a line graph depicting the compactibility of tablets having Formulations F138-F140 (containing 30 mg vamolorone) as prepared as described in Example 6d. [0170] FIG.31 is a line graph depicting the tabletability of tablets having Formulations F138-F140 (containing 30 mg vamolorone) as prepared as described in Example 6d. [0171] FIG.32 is a line graph depicting the disintegration time of tablets having Formulations F138-F140 (containing 30 mg vamolorone) as prepared as described in Example 6d. [0172] FIG.33 is a line graph depicting the compressibility of tablets having Formulations F138-F140 (containing 150 mg vamolorone) as prepared as described in Example 6d. [0173] FIG.34 is a line graph depicting the compactibility of tablets having Formulations F138-F140 (containing 150 mg vamolorone) as prepared as described in Example 6d.
[0174] FIG.35 is a line graph depicting the tabletability of tablets having Formulations F138-F140 (containing 150 mg vamolorone) as prepared as described in Example 6d. [0175] FIG.36 is a line graph depicting the disintegration time of tablets having Formulations F138-F140 (containing 150 mg vamolorone) as prepared as described in Example 6d. [0176] FIG.37 is an X-ray powder diffraction (XPRD) pattern of crystalline vamorolone Form I. DETAILED DESCRIPTION [0177] The headings provided herein are not limitations of the various embodiments of the disclosure, which can be defined by reference to the specification as a whole. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims. Definitions [0178] For convenience, the meaning of some terms and phrases used in the specification, examples, and appended claims are provided below. Unless stated otherwise, or implicit from context, the following terms and phrases include the meanings provided below. The definitions are provided to aid in describing particular embodiments, and are not intended to limit the claimed technology, because the scope of the technology is limited only by the claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this technology belongs. If there is an apparent discrepancy between the usage of a term in the art and its definition provided herein, the definition provided within the specification will control. [0179] The indefinite articles “a” and “an” to describe an element or component means that one or at least one of these elements or components is present. Although these articles are conventionally employed to signify that the modified noun is a singular noun, as used herein the articles “a” and “an” also include the plural, unless otherwise stated in specific instances. Similarly, the definite article “the,” as used herein, also signifies that the modified noun can be singular or plural, again unless otherwise stated in specific instances.
[0180] As used herein, the term “about” used with numerical values means “within 10% of the stated value,” unless expressly noted otherwise. For example, “about 5 wt%” means from 4.5 wt% to 5.5 wt%. [0181] As used herein, the term “wt%” refers to the mass percentage of one component in a composition relative to the combined mass of all components in the composition. For example, the wt% of component A in a composition consisting of 1 g of component A, 4 g of component B, and 5 g of component C is 1 g/(1 g + 4 g + 5 g) x 100% = 10 wt%. [0182] The term “pharmaceutically acceptable,” as applied to carriers, excipients, or other components that can be used in the compositions described herein, refer to carriers, excipients, or other components that are nontoxic to recipients at the dosages and concentrations employed. [0183] As used herein, the terms “comprises,” “comprising,” “having,” “including,” “containing,” and the like are open-ended terms meaning “including, but not limited to.” To the extent a given aspect disclosed herein “comprises” certain elements, it should be understood that present disclosure also specifically contemplates and discloses aspects that “consist essentially of” those elements and that “consist of” those elements. [0184] As used herein the terms “consists essentially of,” “consisting essentially of,” and the like are to be construed as a semi-closed terms, meaning that no other ingredients which materially affect the basic and novel characteristics of an aspect are included. [0185] As used herein, the terms “consists of,” “consisting of,” and the like are to be construed as closed terms, such that an aspect “consisting of” a particular set of elements excludes any element, step, or ingredient not specified in the aspect. [0186] The terms “treat,” “treating,” and “treatment” refer to any indicia of success in the treatment or amelioration of an injury, disease, or condition, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the injury, disease, or condition more tolerable to the patient; slowing in the rate of degeneration or decline; or improving a patient’s physical or mental well-being. The treatment or amelioration of symptoms can be based on objective or subject parameters, including the results of a physical examination, neuropsychiatric examinations, or psychiatric evaluation. [0187] As used herein, the term “Cmax” refers to the maximum serum concentration achieved by a drug in a subject’s body after the drug has been administered to the subject.
[0188] As used herein, the term “Tmax” refers to the time after administration of a drug to a subject at which Cmax is observed in the subject. [0189] As used herein, the term “AUC24” refers to the definite integral, i.e., area under the curve, of a serum concentration of a drug in a subject’s body as a function of time from 0 to 24 hours, and is indicative of the subject’s drug exposure over 24 hours. Pharmaceutical Compositions Vamorolone [0190] The present disclosure provides pharmaceutical compositions comprising vamorolone. Vamorolone is a synthetic corticosteroid and has the following structure:
. [0191] Vamorolone’s full chemical name is [17α,21-dihydroxy-16α-methyl-pregna- 1,4,9(11)-triene-3,20-dione]. Vamorolone is marketed under the trade name AGAMREE®. Other names for vamorolone include 16α-methyl-9,11-dehydro prednisolone and VBP-15. Vamorolone’s CAS registry number is 13209-41-1. [0192] Vamorolone can be an amorphous solid or a crystalline solid. Crystalline forms of vamorolone include vamorolone Forms I-VIII. In some aspects, vamorolone can be vamorolone Form I. In some aspects, vamorolone Form I is characterized by an X-ray powder diffraction pattern comprising peaks, in terms of ° 2θ, at about 11.9, about 13.7, about 16.1, and about 18.3 when measured with Cu Kα radiation. In some aspects, vamorolone Form I is characterized by an X-ray powder diffraction pattern comprising peaks, in terms of ° 2θ, at about 11.9, about 13.7, about 14.4, about 14.8, about 16.1, about 17.0, and about 18.3 when measured with Cu Kα radiation. In some aspects, vamorolone Form I is characterized by an X-ray powder diffraction pattern substantially similar to FIG.37. Vamorolone Form I is disclosed in U.S. Patent No.11,382,922, which is incorporated herein by reference in its entirety. Vamorolone Forms II-VIII are disclosed in U.S. Application Publication No.2023/0002439, which is incorporated herein by reference in its entirety.
Amorphous Solid Dispersions [0193] Amorphous solid dispersions are compositions in which an amorphous active pharmaceutical ingredient, e.g., vamorolone, is dispersed throughout a polymer matrix. Amorphous solid dispersions can increase the solubility of the amorphous active pharmaceutical ingredient, which can lead to improved pharmacokinetic properties. [0194] Amorphous solid dispersions can be prepared by numerous methods, including, but not limited to, hot melt extrusion, twin screw melt granulation, high shear melt granulation, or spray drying. These methods can provide the amorphous solid dispersion as a plurality of granules and/or pellets, which can be further blended with one or more pharmaceutically acceptable excipients and further processed, e.g., by compressing the mixture into a tablet or filling the mixture into a capsule, to provide a solid oral dosage form. [0195] Accordingly, and in certain embodiments, the present disclosure provides a pharmaceutical composition comprising: a) an amorphous solid dispersion comprising amorphous vamorolone and a pharmacuetuically acceptable polymer; and b) one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is a solid oral dosage form. [0196] In some aspects, the amorphous solid dispersion can further comprise crystalline vamorolone, i.e., vamorolone can be present as a mixture of amorphous and crystalline vamorolone. In some aspects, the crystalline vamorolone can comprise crystalline vamorolone Form I. In some aspects, the amorphous solid dispersion can comprise about 0.001 wt%, about 0.01 wt%, about 0.1 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 12 wt%, about 14 wt%, about 16 wt%, about 18 wt%, or about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, wherein the remaining vamorolone present in the amorphous solid dispersion is amorphous. In some aspects, the amorphous solid dispersion can comprise from about 0.001 wt% to about 0.01 wt%, from about 0.001 wt% to about 0.1 wt%, from about 0.001 wt% to about 1 wt%, from about 0.001 wt% to about 3 wt%, from about 0.001 wt% to about 5 wt%, from about 0.001 wt% to about 10 wt%, from about 0.001 wt% to about 15 wt%, from about 0.001 wt% to about 20 wt%, from about 0.01 wt% to about 0.1 wt%, from about 0.01 wt% to about 1 wt%, from about 0.01 wt% to about 3 wt%, from about 0.01 wt% to about 5 wt%, from about
0.01 wt% to about 10 wt%, from about 0.01 wt% to about 15 wt%, from about 0.01 wt% to about 20 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 10 wt%, from about 3 wt% to about 15 wt%, from about 3 wt% to about 20 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, or from about 15 wt% to about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, wherein the remaining vamorolone present in the amorphous solid dispersion is amorphous. [0197] In certain aspects, the amorphous solid dispersion comprising amorphous vamorolone and the pharmaceutically acceptable polymer can futher comprise at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. [0198] In certain aspects, the amorphous solid dispersion comprising amorphous vamorolone, crystalline vamorolone, e.g., crystalline vamorolone Form I, and the pharmaceutically acceptable polymer can futher comprise at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. [0199] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, a polymer having a wt% as described below, and optionally at least one of a plasticizer having a wt% as described below, a surfactant having a wt% as described below, a solubilizing agent having a wt% as described below, and a filler having a wt% as described below. In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt%
to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, with the remainder comprising the polymer, and optionally, at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. [0200] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, from about 0.001 wt% to about 0.01 wt%, from about 0.001 wt% to about 0.1 wt%, from about 0.001 wt% to about 1 wt%, from about 0.001 wt% to about 3 wt%, from about 0.001 wt% to about 5 wt%, from about 0.001 wt% to about 10 wt%, from about 0.001 wt% to about 15 wt%, from about 0.001 wt% to about 20 wt%, from about 0.01 wt% to about 0.1 wt%, from about 0.01 wt% to about 1 wt%, from about 0.01 wt% to about 3 wt%, from about 0.01 wt% to about 5 wt%, from about 0.01 wt% to about 10 wt%, from about 0.01 wt% to about 15 wt%, from about 0.01 wt% to about 20 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt%
to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 10 wt%, from about 3 wt% to about 15 wt%, from about 3 wt% to about 20 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, or from about 15 wt% to about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, a polymer having a wt% as described below, and optionally at least one of a plasticizer having a wt% as described below, a surfactant having a wt% as described below, a solubilizing agent having a wt% as described below, and a filler having a wt% as described below. [0201] In some aspects, the amorphous solid dispersion can comprise about 80 wt% amorphous vamorolone with the remainder comprising the polymer, and optionally, at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. In some aspects, the amorphous solid dispersion can comprise about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% amorphous vamorolone, with the remainder comprising the polymer, and optionally, at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. [0202] In some aspects, the amorphous solid dispersion can comprise about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% amorphous vamorolone and about 0.001 wt%, about 0.01 wt%, about 0.1 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 12 wt%, about 14 wt%, about 16 wt%, about 18 wt%, or about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, with the remainder comprising the polymer, and optionally, at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. [0203] In some aspects, the pharmaceutical composition can comprise from about 5 mg to about 300 mg amorphous vamorolone. In some aspects, the pharmaceutical
composition can comprise from about 5 mg to about 20 mg, from about 5 mg to about 30 mg, from about 5 mg to about 50 mg, from about 5 mg to about 75 mg, from about 5 mg to about 100 mg, from about 5 mg to about 150 mg, from about 5 mg to about 200 mg, from about 5 mg to about 250 mg, from about 5 mg to about 300 mg, from about 10 mg to about 30 mg, from about 10 mg to about 50 mg, from about 10 mg to about 75 mg, from about 10 mg to about 100 mg, from about 10 mg to about 150 mg, from about 10 mg to about 200 mg, from about 10 mg to about 250 mg, from about 10 mg to about 300 mg, from about 30 mg to about 50 mg, from about 30 mg to about 75 mg, from about 30 mg to about 100 mg, from about 30 mg to about 150 mg, from about 30 mg to about 200 mg, from about 30 mg to about 250 mg, from about 30 mg to about 300 mg, from about 50 mg to about 75 mg, from about 50 mg to about 100 mg, from about 50 mg to about 150 mg, from about 50 mg to about 200 mg, from about 50 mg to about 250 mg, from about 50 mg to about 300 mg, from about 75 mg to about 100 mg, from about 75 mg to about 150 mg, from about 75 mg to about 200 mg, from about 75 mg to about 250 mg, from about 75 mg to about 300 mg, from about 100 mg to about 150 mg, from about 100 mg to about 200 mg, from about 100 mg to about 250 mg, from about 100 mg to about 300 mg, from about 100 mg to about 350 mg, from about 100 mg to about 400 mg, from about 150 mg to about 200 mg, from about 150 mg to about 250 mg, from about 150 mg to about 300 mg, from about 200 mg to about 250 mg, from about 200 mg to about 300 mg, from about 200 mg to about 350 mg, from about 200 mg to about 400 mg, or from about 250 mg to about 300 mg amorphous vamorolone, with the remainder comprising the polymer, and optionally, at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. [0204] In some aspects, the pharmaceutical composition can comprise about 150 mg amorphous vamorolone with the remainder comprising the polymer, and optionally, at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. In some aspects, the pharmaceutical composition can comprise about 5 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, or about 300 mg amorphous vamorolone. [0205] In some aspects, the amorphous solid dispersion can comprise from about 5 mg to about 300 mg amorphous vamorolone. In some aspects, the amorphous solid dispersion can comprise from about 5 mg to about 20 mg, from about 5 mg to about 30 mg, from
about 5 mg to about 50 mg, from about 5 mg to about 75 mg, from about 5 mg to about 100 mg, from about 5 mg to about 150 mg, from about 5 mg to about 200 mg, from about 5 mg to about 250 mg, from about 5 mg to about 300 mg, from about 10 mg to about 30 mg, from about 10 mg to about 50 mg, from about 10 mg to about 75 mg, from about 10 mg to about 100 mg, from about 10 mg to about 150 mg, from about 10 mg to about 200 mg, from about 10 mg to about 250 mg, from about 10 mg to about 300 mg, from about 30 mg to about 50 mg, from about 30 mg to about 75 mg, from about 30 mg to about 100 mg, from about 30 mg to about 150 mg, from about 30 mg to about 200 mg, from about 30 mg to about 250 mg, from about 30 mg to about 300 mg, from about 50 mg to about 75 mg, from about 50 mg to about 100 mg, from about 50 mg to about 150 mg, from about 50 mg to about 200 mg, from about 50 mg to about 250 mg, from about 50 mg to about 300 mg, from about 75 mg to about 100 mg, from about 75 mg to about 150 mg, from about 75 mg to about 200 mg, from about 75 mg to about 250 mg, from about 75 mg to about 300 mg, from about 100 mg to about 150 mg, from about 100 mg to about 200 mg, from about 100 mg to about 250 mg, from about 100 mg to about 300 mg, from about 100 mg to about 350 mg, from about 100 mg to about 400 mg, from about 150 mg to about 200 mg, from about 150 mg to about 250 mg, from about 150 mg to about 300 mg, from about 200 mg to about 250 mg, from about 200 mg to about 300 mg, from about 200 mg to about 350 mg, from about 200 mg to about 400 mg, or from about 250 mg to about 300 mg amorphous vamorolone, with the remainder comprising the polymer, and optionally, at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. [0206] In some aspects, the amorphous solid dispersion can comprise about 150 mg amorphous vamorolone with the remainder comprising the polymer, and optionally, at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. In some aspects, the amorphous solid dispersion can comprise about 5 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, or about 300 mg amorphous vamorolone, with the remainder comprising the polymer, and optionally, at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. [0207] In some aspects, the polymer in the amorphous solid dispersion can be hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as
hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. [0208] In some aspects, as stated above, poly(ethylene oxide) can have any molecular weight, e.g., from about 3,000 to about 20,000,000. In some aspects, poly(ethylene oxide) can have a molecular weight of from about 2,000 to about 3,500, from about 2,000 to about 4,000, from about 2,000 to about 5,000, from about 2,000 to about 5,500, from about 2,000 to about 6,000, from about 2,000 to about 7,000, from about 2,000 to about 8,000, from about 2,000 to about 10,000, from about 2,000 to about 50,000, from about 2,000 to about 100,000, from about 2,000 to about 1,000,000, from about 2,000 to about 5,000,000, from about 2,000 to about 20,000,000, from about 3,000 to about 5,000, from about 3,000 to about 5,500, from about 3,000 to about 6,000, from about 3,000 to about 7,000, from about 3,000 to about 8,000, from about 3,000 to about 10,000, from about 3,000 to about 50,000, from about 3,000 to about 100,000, from about 3,000 to about 1,000,000, from about 3,000 to about 5,000,000, from about 3,000 to about 20,000,000, from about 5,000 to about 6,000, from about 5,000 to about 7,000, from about 5,000 to about 8,000, from about 5,000 to about 10,000, from about 5,000 to about 50,000, from about 5,000 to about 100,000, from about 5,000 to about 1,000,000, from about 5,000 to about 5,000,000, from about 5,000 to about 20,000,000, about 6,000 to about 8,000, from about 6,000 to about 10,000, from about 6,000 to about 50,000, from about 6,000 to about 100,000, from about 6,000 to about 1,000,000, from about 6,000 to about 5,000,000, from about 6,000 to about 20,000,000, from about 8,000 to about 10,000, from about 8,000 to about 50,000, from about 8,000 to about 100,000, from about 8,000 to about 1,000,000, from about 8,000 to about 5,000,000, from about 8,000 to about 20,000,000, from about
10,000 to about 50,000, from about 10,000 to about 100,000, from about 10,000 to about 1,000,000, from about 10,000 to about 5,000,000, from about 10,000 to about 20,000,000, from about 100,000 to about 1,000,000, from about 100,000 to about 5,000,000, or from about 5,000,000 to about 20,000,000. [0209] In some aspects, poly(ethylene oxide) can have a molecular weight of about 3,500. In some aspects, poly(ethylene oxide) can have a molecular weight of about 2,000, about 2,500, about 3,000, about 3,500, about 4,000, about 4,500, about 5,000, about 5,500, about 6,000, about 6,500, about 7,000, about 7,500, about 8,000, about 9,500, about 10,000, about 20,000, about 50,000, about 1,000,000, about 2,000,000, about 5,000,000, about 7,500,000, about 10,000,000, about 15,000,000, or about 20,000,000. [0210] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 95 wt% to about 15 wt% of the polymer, and optionally, at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. In particular, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone and from about 5 wt% to about 85 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose
(HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, or from about 45 wt% to about 55 wt% amorphous vamorolone and from about 45 wt% to about 85 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or any combination of the foregoing. [0211] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 0.001 wt% to about 20 wt%, crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 95 wt% to about 15 wt% of the polymer, and optionally, at least one of a plasticizer, a surfactant, a solubilizing agent, and a filler. In particular, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt%
to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, from about 0.001 wt% to about 0.01 wt%, from about 0.001 wt% to about 0.1 wt%, from about 0.001 wt% to about 1 wt%, from about 0.001 wt% to about 3 wt%, from about 0.001 wt% to about 5 wt%, from about 0.001 wt% to about 10 wt%, from about 0.001 wt% to about 15 wt%, from about 0.001 wt% to about 20 wt%, from about 0.01 wt% to about 0.1 wt%, from about 0.01 wt% to about 1 wt%, from about 0.01 wt% to about 3 wt%, from about 0.01 wt% to about 5 wt%, from about 0.01 wt% to about 10 wt%, from about 0.01 wt% to about 15 wt%, from about 0.01 wt% to about 20 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 10 wt%, from about 3 wt% to about 15 wt%, from about 3 wt% to about 20 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, or from about 15 wt% to about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, and from about 5 wt% to about 85 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate
phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. [0212] In some aspects, the amorphous solid dispersion can comprise from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer
(SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. [0213] In some aspects, the amorphous solid dispersion can comprise about 80 wt% amorphous vamorolone and about 20 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. In some aspects, the amorphous solid dispersion can comprise about 15 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, or about 90 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate-
polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. [0214] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 95 wt% amorphous vamorolone and from about 5 wt% to about 85 wt% of a polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. [0215] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 0.001 wt% to about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, and from about 5 wt% to about 85 wt% of a polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose
acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. [0216] In some aspects, the pharmaceutical composition can comprise an amorphous solid dispersion comprising from about 5 mg to about 20 mg, from about 5 mg to about 30 mg, from about 5 mg to about 50 mg, from about 5 mg to about 75 mg, from about 5 mg to about 100 mg, from about 5 mg to about 150 mg, from about 5 mg to about 200 mg, from about 5 mg to about 250 mg, from about 5 mg to about 300 mg, from about 10 mg to about 30 mg, from about 10 mg to about 50 mg, from about 10 mg to about 75 mg, from about 10 mg to about 100 mg, from about 10 mg to about 150 mg, from about 10 mg to about 200 mg, from about 10 mg to about 250 mg, from about 10 mg to about 300 mg, from about 30 mg to about 50 mg, from about 30 mg to about 75 mg, from about 30 mg to about 100 mg, from about 30 mg to about 150 mg, from about 30 mg to about 200 mg, from about 30 mg to about 250 mg, from about 30 mg to about 300 mg, from about 50 mg to about 75 mg, from about 50 mg to about 100 mg, from about 50 mg to about 150 mg, from about 50 mg to about 200 mg, from about 50 mg to about 250 mg, from about 50 mg to about 300 mg, from about 75 mg to about 100 mg, from about 75 mg to about 150 mg, from about 75 mg to about 200 mg, from about 75 mg to about 250 mg, from about 75 mg to about 300 mg, from about 100 mg to about 150 mg, from about 100 mg to about 200 mg, from about 100 mg to about 250 mg, from about 100 mg to about 300 mg, from about 100 mg to about 350 mg, from about 100 mg to about 400 mg, from about 150 mg to about 200 mg, from about 150 mg to about 250 mg, from about 150 mg to about 300 mg, from about 200 mg to about 250 mg, from about 200 mg to about 300 mg, from about 200 mg to about 350 mg, from about 200 mg to about 400 mg, or from about 250 mg to about 300 mg amorphous vamorolone, which can be from about 1 wt% to about 5 wt%, from about 1 wt% to about 15 wt%, from about 5 wt% to about 15 wt%,
from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% of the total mass of the amorphous solid dispersion, and from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the polymer relative to the total mass of the amorphous solid dispersion, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl
methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. [0217] In some aspects, the amorphous solid dispersion can further comprise a plasticizer. In some aspects, the plasticizer can comprise a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing. [0218] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, about 95 wt% to about 15 wt % of the polymer and about 0.1 wt% to about 25 wt% of the plasticizer. In some aspects, the amorphous solid dispersion can comprise from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 25 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 25 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 25 wt%, from about 15 wt% to about 20 wt%, from about 15 wt% to about 25 wt%, or from about 20 wt% to about 25 wt% of the plasticizer.
[0219] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl
methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, and from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 25 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 25 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 25 wt%, from about 15 wt% to about 20 wt%, from about 15 wt% to about 25 wt%, or from about 20 wt% to about 25 wt% of the plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing. In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, or from about 45 wt% to about 55 wt% amorphous vamorolone, from about 45
wt% to about 85 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or any combination of the foregoing, and from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, or from about 5 wt% to about 10 wt% of the plasticizer, wherein the plasticizer is poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500. [0220] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, from about 0.001 wt% to about 0.01 wt%, from about 0.001 wt% to about 0.1 wt%, from about 0.001 wt% to about 1 wt%, from about 0.001 wt% to about 3 wt%, from about 0.001 wt% to about 5 wt%, from about 0.001 wt% to about 10 wt%, from about 0.001 wt% to about 15 wt%, from about 0.001 wt% to about 20 wt%, from about 0.01 wt% to about 0.1 wt%, from about 0.01 wt% to about 1 wt%, from about 0.01 wt%
to about 3 wt%, from about 0.01 wt% to about 5 wt%, from about 0.01 wt% to about 10 wt%, from about 0.01 wt% to about 15 wt%, from about 0.01 wt% to about 20 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 10 wt%, from about 3 wt% to about 15 wt%, from about 3 wt% to about 20 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, or from about 15 wt% to about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-
64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, and from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 25 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 25 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 25 wt%, from about 15 wt% to about 20 wt%, from about 15 wt% to about 25 wt%, or from about 20 wt% to about 25 wt% of the plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing. [0221] In some aspects, the amorphous solid dispersion can comprise about 10 wt% of the plasticizer. In some aspects, the amorphous solid dispersion can comprise about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 11 wt%, about 12 wt%, about 13 wt%, about 14 wt%, about 15 wt%, about 16 wt%, about 17 wt%, about 18 wt%, about 19 wt%, about 20 wt%, about 21 wt%, about 22 wt%, about 23 wt%, about 24 wt%, or about 25 wt% of the plasticizer. [0222] In some aspects, the amorphous solid dispersion can comprise about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%,
about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% amorphous vamorolone, about 15 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, or about 90 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, and about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 11 wt%, about 12 wt%, about 13 wt%, about 14 wt%, about 15 wt%, about 16 wt%, about 17 wt%, about 18 wt%, about 19 wt%, about 20 wt%, about 21 wt%, about 22 wt%, about 23 wt%, about 24 wt%, or about 25 wt% of the plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing. [0223] In some aspects, the amorphous solid dispersion can comprise about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%,
about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% amorphous vamorolone, about 0.001 wt%, about 0.01 wt%, about 0.1 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 12 wt%, about 14 wt%, about 16 wt%, about 18 wt%, or about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, about 15 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, or about 90 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K- 17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam- polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid- ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, and about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 11 wt%, about 12 wt%, about 13 wt%, about 14 wt%, about 15 wt%, about 16 wt%, about 17 wt%, about 18 wt%, about 19 wt%, about 20 wt%, about 21 wt%, about 22 wt%, about 23 wt%, about 24 wt%, or about 25 wt% of the plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing.
[0224] In some aspects, the amorphous solid dispersion can comprise 15 wt% to about 95 wt% amorphous vamorolone, about 95 wt% to about 15 wt % of the polymer, about 0.1 wt% to 25 wt% of the plasticizer, and can further comprise a surfactant. In some aspects, the surfactant can comprise sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing. [0225] In some aspects, the amorphous solid dispersion can comprise about 15 wt% to about 95 wt% amorphous vamorolone, about 95 wt% to about 15 wt % of the polymer, about 0.1 wt% to 25 wt% of the plasticizer, and from about 0.1 wt% to about 10 wt% of the surfactant. In some aspects, the amorphous solid dispersion can comprise from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the surfactant. [0226] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from
about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or
any combination of the foregoing, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 25 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 25 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 25 wt%, from about 15 wt% to about 20 wt%, from about 15 wt% to about 25 wt%, or from about 20 wt% to about 25 wt% of the plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the surfactant, wherein the surfactant is sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing. [0227] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt%
to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, from about 0.001 wt% to about 0.01 wt%, from about 0.001 wt% to about 0.1 wt%, from about 0.001 wt% to about 1 wt%, from about 0.001 wt% to about 3 wt%, from about 0.001 wt% to about 5 wt%, from about 0.001 wt% to about 10 wt%, from about 0.001 wt% to about 15 wt%, from about 0.001 wt% to about 20 wt%, from about 0.01 wt% to about 0.1 wt%, from about 0.01 wt% to about 1 wt%, from about 0.01 wt% to about 3 wt%, from about 0.01 wt% to about 5 wt%, from about 0.01 wt% to about 10 wt%, from about 0.01 wt% to about 15 wt%, from about 0.01 wt% to about 20 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 10 wt%, from about 3 wt% to about 15 wt%, from about 3 wt% to about 20 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, or from about 15 wt% to about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt%
to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 25 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 25 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 25 wt%, from about 15 wt% to about 20 wt%, from about 15 wt% to about 25 wt%, or from about
20 wt% to about 25 wt% of the plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the surfactant, wherein the surfactant is sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing. [0228] In some aspects, the amorphous solid dispersion can comprise about 5 wt% of the surfactant. In some aspects, the amorphous solid dispersion can comprise about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt% of the surfactant. [0229] In some aspects, the amorphous solid dispersion can comprise about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% amorphous vamorolone, about 15 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, or about 90 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade,
e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 11 wt%, about 12 wt%, about 13 wt%, about 14 wt%, about 15 wt%, about 16 wt%, about 17 wt%, about 18 wt%, about 19 wt%, about 20 wt%, about 21 wt%, about 22 wt%, about 23 wt%, about 24 wt%, or about 25 wt% of the plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing, and about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt% of the surfactant, wherein the surfactant is sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing. [0230] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45
wt%, from about 15 wt% to about 55 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, or from about 45 wt% to about 55 wt% amorphous vamorolone, from about 45 wt% to about 85 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or any combination of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the surfactant, wherein the surfactant is a poloxamer, e.g., P188 or P407; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing. [0231] In some aspects, the amorphous solid dispersion can comprise about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% amorphous vamorolone, about 0.001 wt%, about 0.01 wt%, about 0.1 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 12 wt%, about 14 wt%, about 16 wt%, about 18 wt%, or about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, about 15 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55
wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, or about 90 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K- 17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam- polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid- ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 11 wt%, about 12 wt%, about 13 wt%, about 14 wt%, about 15 wt%, about 16 wt%, about 17 wt%, about 18 wt%, about 19 wt%, about 20 wt%, about 21 wt%, about 22 wt%, about 23 wt%, about 24 wt%, or about 25 wt% of the plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing, and about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt% of the surfactant, wherein the surfactant is sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or
GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing. [0232] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 5 wt% to about 85 wt% of a polymer, optionally from about 0.1 wt% to about 25 wt% of a plasticizer, and optionally from about 0.1 wt% to about 10 wt% of a surfactant. In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 50 wt% amorphous vamorolone, from about 40 wt% to about 70 wt% of a polymer, optionally from about 0.1 wt% to about 25 wt% of a plasticizer, and optionally from about 0.1 wt% to about 10 wt% of a surfactant. [0233] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 0.001 wt% to about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 5 wt% to about 85 wt% of a polymer, optionally from about 0.1 wt% to about 25 wt% of a plasticizer, and optionally from about 0.1 wt% to about 10 wt% of a surfactant. [0234] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 50 wt% amorphous vamorolone, from about 0.001 wt% to about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 40 wt% to about 70 wt% of a polymer, optionally from about 0.1 wt% to about 25 wt% of a plasticizer, and optionally from about 0.1 wt% to about 10 wt% of a surfactant. [0235] In some aspects, the pharmaceutical composition can comprise an amorphous solid dispersion comprising from about 5 mg to about 300 mg amorphous vamololone, which can be from 1 wt% to about 90 wt% of the total mass of the amorphous solid dispersion, from about 5 wt% to about 85 wt% of a polymer relative to the total mass of the amorphous solid dispersion, optionally from about 0.1 wt% to about 25 wt% of a plasticizer relative to the total mass of the amorphous solid dispersion, and optionally from about 0.1 wt% to about 10 wt% of a surfactant relative to the total mass of the amorphous solid dispersion. [0236] In some aspects, the amorphous solid dispersion can further comprise a solubilizing agent, such as a cyclodextrin. [0237] In some aspects, the amorphous solid dispersion can comprise from about 1 wt% to about 40 wt% of the solubilizing agent. In some aspects, the amorphous solid dispersion can comprise from about 1 wt% to about 5 wt%, from about 1 wt% to about 10
wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 30 wt%, %, from about 5 wt% to about 10 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 40 wt%,%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%,%, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, or from about 30 wt% to about 40 wt% of a solubilizing agent. [0238] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt%
to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 25 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 25 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 25 wt%, from about 15 wt% to about 20 wt%, from about 15 wt% to about 25 wt%, or from about 20 wt% to about 25 wt% of the plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or
erythriol; or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the surfactant, wherein the surfactant is sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing, and from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 30 wt%, %, from about 5 wt% to about 10 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 40 wt%,%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%,%, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, or from about 30 wt% to about 40 wt% of the solubilizing agent, e.g., a cyclodextrin. [0239] In some aspects, the amorphous solid dispersion can comprise about 10 wt% of a solubilizing agent. In some aspects, the amorphous solid dispersion can comprise about 1 wt%, about 5 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, or about 40 wt% of a solubilizing agent. [0240] In some aspects, the amorphous solid dispersion can comprise about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% amorphous vamorolone, about 15 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, or about 90 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade,
e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 11 wt%, about 12 wt%, about 13 wt%, about 14 wt%, about 15 wt%, about 16 wt%, about 17 wt%, about 18 wt%, about 19 wt%, about 20 wt%, about 21 wt%, about 22 wt%, about 23 wt%, about 24 wt%, or about 25 wt% of the plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing, about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt% of the surfactant, wherein the surfactant is sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing, and about 1 wt%, about 5 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, or about 40 wt% of the solubilizing agent, e.g., a cyclodextrin.
[0241] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 5 wt% to about 85 wt% of a polymer, optionally from about 0.1 wt% to about 25 wt% of a plasticizer, optionally from about 0.1 wt% to about 10 wt% of a surfactant, and optionally from about 1 wt% to about 40 wt% of a solubilizing agent. [0242] In some aspects, the pharmaceutical composition can comprise an amorphous solid dispersion comprising from about 5 mg to about 300 mg amorphous vamorolone, which can be from about 1 wt% to about 90 wt% of the total mass of the amorphous solid dispersion, from about 5 wt% to about 85 wt% of a polymer relative to the total mass of the amorphous solid dispersion, optionally from about 0.1 wt% to about 25 wt% of a plasticizer relative to the total mass of the amorphous solid dispersion, optionally from about 0.1 wt% to about 10 wt% of a surfactant relative to the total mass of the amorphous solid dispersion, and optionally from about 1 wt% to about 40 wt% of a solubilizing agent relative to the total mass of the amorphous solid dispersion. [0243] In some aspects, the amorphous solid dispersion can further comprise a filler. In some aspects, the filler can comprise microcrystalline cellulose (e.g., standard (PH grades), fibrous (KG grades), or mixed (UF grades)), silicified microcrystalline cellulose, carboxymethylcellulose sodium, methylcellulose, hydroxyethylmethyl cellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, povidone, copovidone, lactose monohydrate, lactose anhydrous, mannitol, sucrose, dextrates (EMDEX® or CAMDEX®), maltodextrin, polydextrose, starch, pregelatinized starch (partially or fully gelatinized), hydroxypropyl starch, carbomer, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate and maltodextrin, polycarbophil, or a combination of any of the foregoing. [0244] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% of a filler. In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%, from about 10 wt% to about 50 wt%, from about 10 wt% to about 60 wt%, from about 10 wt% to about 70 wt%, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from
about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 30 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, or from about 70 wt% to about 80 wt% of a filler. [0245] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt%
to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 25 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 25 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 25 wt%, from about 15 wt% to about 20 wt%, from about 15 wt% to about 25 wt%, or from about 20 wt% to about 25 wt% of the plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or
erythriol; or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the surfactant, wherein the surfactant is sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing, optionally from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 30 wt%, %, from about 5 wt% to about 10 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 40 wt%,%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%,%, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, or from about 30 wt% to about 40 wt% of the solubilizing agent, e.g., a cyclodextrin, and from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%, from about 10 wt% to about 50 wt%, from about 10 wt% to about 60 wt%, from about 10 wt% to about 70 wt%, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 30 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, or from about 70 wt% to about 80 wt% of a filler, wherein the filler is microcrystalline cellulose (e.g., standard (PH grades),
fibrous (KG grades), or mixed (UF grades)), silicified microcrystalline cellulose, carboxymethylcellulose sodium, methylcellulose, hydroxyethylmethyl cellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, povidone, copovidone, lactose monohydrate, lactose anhydrous, mannitol, sucrose, dextrates (EMDEX® or CAMDEX®), maltodextrin, polydextrose, starch, pregelatinized starch (partially or fully gelatinized), hydroxypropyl starch, carbomer, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate and maltodextrin, polycarbophil, or a combination of any of the foregoing. [0246] In some aspects, the amorphous solid dispersion can comprise about 20 wt% of a filler. In some aspects, the amorphous solid dispersion can comprise about 10 wt%, about 15 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, or about 80 wt% of a filler. [0247] In some aspects, the amorphous solid dispersion can comprise about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% amorphous vamorolone, about 15 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, or about 90 wt% of the polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular
aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 11 wt%, about 12 wt%, about 13 wt%, about 14 wt%, about 15 wt%, about 16 wt%, about 17 wt%, about 18 wt%, about 19 wt%, about 20 wt%, about 21 wt%, about 22 wt%, about 23 wt%, about 24 wt%, or about 25 wt% of the plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing, about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt% of the surfactant, wherein the surfactant is sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing, optionally about 1 wt%, about 5 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, or about 40 wt% of the solubilizing agent, e.g., a cyclodextrin, and about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, or about 80 wt% of a filler, wherein the filler is microcrystalline cellulose (e.g., standard (PH grades), fibrous (KG grades), or mixed (UF grades)), silicified microcrystalline cellulose, carboxymethylcellulose sodium, methylcellulose, hydroxyethylmethyl cellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, povidone, copovidone, lactose monohydrate, lactose anhydrous, mannitol, sucrose, dextrates (EMDEX® or CAMDEX®), maltodextrin, polydextrose, starch, pregelatinized starch (partially or fully gelatinized), hydroxypropyl starch, carbomer, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate
anhydrous, coprocessed dicalcium phosphate and maltodextrin, polycarbophil, or a combination of any of the foregoing. [0248] In some aspects, the amorphous solid dispersion can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 5 wt% to about 85 wt% of a polymer, optionally from about 0.1 wt% to about 25 wt% of a plasticizer, optionally from about 0.1 wt% to about 10 wt% of a surfactant, optionally from about 1 wt% to about 40 wt% of a solubilizing agent, and optionally from about 10 wt% to about 80 wt% of a filler. [0249] In some aspects, the pharmaceutical composition can comprise an amorphous solid dispersion comprising from about 5 mg to about 300 mg amorphous vamorolone, which can be from about 1 wt% to about 90 wt% of the total mass of the amorphous solid dispersion, from about 5 wt% to about 85 wt% of a polymer relative to the total mass of the amorphous solid dispersion, optionally from about 0.1 wt% to about 25 wt% of a plasticizer relative to the total mass of the amorphous solid dispersion, optionally from about 0.1 wt% to about 10 wt% of a surfactant relative to the total mass of the amorphous solid dispersion, optionally from about 1 wt% to about 40 wt% of a solubilizing agent relative to the total mass of the amorphous solid dispersion, and optionally from about 10 wt% to about 80 wt% of a filler relative to the total mass of the amorphous solid dispersion. [0250] In some aspects, any of the amorphous solid dispersions described above can be provided as a plurality of granules or pellets. In some aspects, the amorphous solid dispersion is provided as a plurality of granules or pellets and can comprise from about 15 wt% to about 95 wt% amorphous vamorolone and from about 95 wt% to about 15 wt% of a polymer. In some aspects, the amorphous solid dispersion is provided as a plurality of granules or pellets and can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 95 wt% to about 15 wt% of a polymer, and from about 0.1 wt% to about 25 wt% of a plasticizer. In some aspects, the amorphous solid dispersion is provided as a plurality of granules or pellets and can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 95 wt% to about 15 wt% of a polymer, from about 0.1 wt% to about 25 wt% of a plasticizer, and from about 0.1 wt% to about 10 wt % of a surfactant. In some aspects, the amorphous solid dispersion is provided as a plurality of granules or pellets and can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 95 wt% to about 15 wt% of a polymer, from about
0.1 wt% to about 25 wt% of a plasticizer, from about 0.1 wt% to about 10 wt % of a surfactant, and from about 1 wt% to about 40 wt% of a solubilizing agent. In some aspects, the amorphous solid dispersion is provided as a plurality of granules or pellets and can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 95 wt% to about 15 wt% of a polymer, from about 0.1 wt% to about 25 wt% of a plasticizer, from about 0.1 wt% to about 10 wt % of a surfactant, from about 1 wt% to about 40 wt% of a solubilizing agent, and from about 10 wt% to about 80 wt% of a filler. [0251] In some aspects, the amorphous solid dispersion is provided as a plurality of granules or pellets and can comprise from about 15 wt% to about 95 wt% amorphous vamorolone and from about 95 wt% to about 15 wt% of a polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. [0252] In some aspects, the amorphous solid dispersion is provided as a plurality of granules or pellets and can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 95 wt% to about 15 wt% of a polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-
64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, and from about 0.1 wt% to about 25 wt% of a plasticizer, wherein the plasticizer is a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing. [0253] In some aspects, the amorphous solid dispersion is provided as a plurality of granules or pellets and can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, from about 95 wt% to about 15 wt% of a polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing, from about 0.1 wt% to about 25 wt% of a plasticizer, wherein the plasticizer is a citrate ester,
e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing, optionally from about 0.1 wt% to about 10 wt % of a surfactant, wherein the surfactant is sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing, optionally from about 1 wt% to about 40 wt% of a solubilizing agent, e.g., cyclodextrin,, and optionally from about 10 wt% to about 80 wt% of a filler, wherein the filler is microcrystalline cellulose (e.g., standard (PH grades), fibrous (KG grades), or mixed (UF grades)), silicified microcrystalline cellulose, carboxymethylcellulose sodium, methylcellulose, hydroxyethylmethyl cellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, povidone, copovidone, lactose monohydrate, lactose anhydrous, mannitol, sucrose, dextrates (EMDEX® or CAMDEX®), maltodextrin, polydextrose, starch, pregelatinized starch (partially or fully gelatinized), hydroxypropyl starch, carbomer, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate and maltodextrin, polycarbophil, or a combination of any of the foregoing. [0254] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the amorphous solid dispersion, optionally one or more diluents having a wt% as described below, optionally one or more disintegrants having a wt% as described below, optionally one or more lubricants having a wt% as described below, optionally one or more flow enhancers having a wt% as described below, optionally one or more suspending agents having a wt% as described below, optionally one or more buffering agents having a wt% as described below, optionally one or more wetting agents having a wt% as described below, optionally one or more preservatives having a wt% as described below, and optionally one or more flavoring agents having a wt% as described below. In some aspects, the pharmaceutical composition can comprise from about 20 wt%
to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 20 wt% to about 90 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 90 wt%, from about 30 wt% to about 95 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 90 wt%, from about 40 wt% to about 95 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 90 wt%, from about 50 wt% to about 95 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 90 wt%, from about 60 wt% to about 95 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 90 wt%, from about 70 wt% to about 95 wt%, from about 80 wt% to about 90 wt%, from about 80 wt% to about 95 wt%, or from about 90 wt% to about 95 wt% of the amorphous solid dispersion. [0255] In some aspects, the pharmaceutical composition can comprise about 80 wt% of the amorphous solid dispersion. In some aspects, the pharmaceutical composition can comprise about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 85 wt%, about 90 wt%, or about 95 wt% of the amorphous solid dispersion. [0256] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the amorphous solid dispersion and optionally from about 5 wt% to about 85 wt% of one or more diluents. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the amorphous solid dispersion, optionally from about 5 wt% to about 85 wt% of one or more diluents, and optionally from about 0.25 wt% to about 10 wt% of one or more disintegrants. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the amorphous solid dispersion, optionally from about 5 wt% to about 85 wt% of one or more diluents, optionally from about 0.25 wt% to about 10 wt% of one or more disintegrants, and optionally from about 0.1 wt% to about 5 wt% of one or more lubricants. In some aspects, the pharmaceutical composition can comprise from about 20
wt% to about 95 wt% of the amorphous solid dispersion, optionally from about 5 wt% to about 85 wt% of one or more diluents, optionally from about 0.25 wt% to about 10 wt% of one or more disintegrants, optionally from about 0.1 wt% to about 5 wt% of one or more lubricants, and optionally from about 0.1 wt% to about 5 wt% of one or more flow enhancers. [0257] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the amorphous solid dispersion and optionally from about 5 wt% to about 80 wt% of one or more suspending agents. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the amorphous solid dispersion, optionally from about 5 wt% to about 80 wt% of one or more suspending agents, and optionally from about 0.1 wt% to about 5 wt% of one or more buffering agents. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the amorphous solid dispersion, optionally from about 5 wt% to about 80 wt% of one or more suspending agents, optionally from about 0.1 wt% to about 5 wt% of one or more buffering agents, and optionally from about 0.1 wt% to about 10 wt% of one or more wetting agents. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the amorphous solid dispersion, optionally from about 5 wt% to about 80 wt% of one or more suspending agents, optionally from about 0.1 wt% to about 5 wt% of one or more buffering agents, optionally from about 0.1 wt% to about 10 wt% of one or more wetting agents, and optionally from about 0.1 wt% to about 5 wt% of one or more preservatives. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the amorphous solid dispersion, optionally from about 5 wt% to about 80 wt% of one or more suspending agents, optionally from about 0.1 wt% to about 5 wt% of one or more buffering agents, optionally from about 0.1 wt% to about 10 wt% of one or more wetting agents, optionally from about 0.1 wt% to about 5 wt% of one or more preservatives, and from about 0.1 wt% to about 5 wt% of one or more flavoring agents. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the amorphous solid dispersion, optionally from about 5 wt% to about 80 wt% of one or more suspending agents, optionally from about 0.1 wt% to about 5 wt% of one or more buffering agents, optionally from about 0.1 wt% to about 10 wt% of one or more wetting agents, optionally from about 0.1 wt% to about 5 wt% of one or more
preservatives, from about 0.1 wt% to about 5 wt% of one or more flavoring agents, and from about 0.1 wt% to about 5 wt% of one or more flow enhancers. [0258] In some aspects, the amorphous solid dispersion can be prepared by hot melt extrusion, twin screw melt granulation, high shear melt granulation, or spray drying. In some aspects, the amorphous solid dispersion can be prepared using methods similar to those described in Examples 1-4b below. [0259] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone, from about 10 wt% to about 80 wt% HPMCAS, optionally from about 0.1 wt% to about 10 wt% of a plasticizer, e.g., triethyl citrate and/or polyethylene glycol (e.g., PEG 400), optionally from about 0.1 wt% to about 5 wt% of a surfactant, e.g., sodium lauryl sulfate, poloxamer (e.g., poloxamer 188), and/or polysorbate 80. [0260] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 30 wt% amorphous vamorolone, from about 70 wt% to about 90 wt% HPMCAS, and from about 0.1 wt% to about 5 wt% of a surfactant, e.g., poloxamer (e.g., poloxamer 188). In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 30 wt% amorphous vamorolone, from about 0.001 wt% to about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 70 wt% to about 90 wt% HPMCAS, and from about 0.1 wt% to about 5 wt% of a surfactant, e.g., poloxamer (e.g., poloxamer 188). [0261] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone, from about 10 wt% to about 80 wt% HPMC, optionally from about 0.1 wt% to about 10 wt% of a plasticizer, e.g., triethyl citrate and/or polyethylene glycol (e.g., PEG 400), optionally from about 0.1 wt% to about 5 wt% of a surfactant, e.g., sodium lauryl sulfate, poloxamer (e.g., poloxamer 188), and/or polysorbate 80. [0262] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone, from about 10 wt% to about 80 wt% povidone (e.g., K-30), optionally from about 0.1 wt% to about 10 wt% of a plasticizer, e.g., triethyl citrate and/or polyethylene glycol (e.g., PEG 400), optionally from about 0.1 wt% to about 5 wt% of a surfactant, e.g., sodium lauryl sulfate, poloxamer (e.g., poloxamer 188), and/or polysorbate 80.
[0263] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 50 wt% amorphous vamorolone, from about 50 wt% to about 90 wt% povidone (e.g., K-30), and about 1 wt% to about 10 wt% of a plasticizer, e.g., polyethylene glycol (e.g., PEG 4000). [0264] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone, from about 10 wt% to about 80 wt% copovidone (e.g., KOLLIDON® VA64), optionally from about 0.1 wt% to about 10 wt% of a plasticizer, e.g., triethyl citrate and/or polyethylene glycol (e.g., PEG 400), optionally from about 0.1 wt% to about 5 wt% of a surfactant, e.g., sodium lauryl sulfate, poloxamer (e.g., poloxamer 188), and/or polysorbate 80. [0265] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 50 wt% amorphous vamorolone, from about 50 wt% to about 90 wt% copovidone (e.g., KOLLIDON® VA64), and from about 1 wt% to about 10 wt% of a plasticizer, e.g., polyethylene glycol (e.g., PEG 4000). In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 50 wt% amorphous vamorolone, from about 0.001 wt% to about 20 wt% crystalline vamorolone, from about 50 wt% to about 90 wt% copovidone (e.g., KOLLIDON® VA64), and from about 1 wt% to about 10 wt% of a plasticizer, e.g., polyethylene glycol (e.g., PEG 4000). [0266] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 50 wt% amorphous vamorolone, from about 50 wt% to about 90 wt% copovidone (e.g., KOLLIDON® VA64), and from about 1 wt% to about 10 wt% of a surfactant, e.g., LABRASOL®, GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01), or a poloxamer, e.g., P188 or P407. In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 50 wt% amorphous vamorolone, from about 0.001 wt% to about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 50 wt% to about 90 wt% copovidone (e.g., KOLLIDON® VA64), and from about 1 wt% to about 10 wt% of a surfactant, e.g., LABRASOL®, GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01), or a poloxamer, e.g., P188 or P407. [0267] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone, from about 10 wt% to about 80 wt% polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (e.g., SOLUPLUS®), optionally from about 0.1 wt% to about 10 wt% of a plasticizer, e.g., triethyl citrate
and/or polyethylene glycol (e.g., PEG 400), optionally from about 0.1 wt% to about 5 wt% of a surfactant, e.g., sodium lauryl sulfate, poloxamer (e.g., poloxamer 188), and/or polysorbate 80. [0268] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 40 wt% amorphous vamorolone, from about 60 wt% to about 90 wt% polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (e.g., SOLUPLUS®), and from about 1 wt% to about 10 wt% of a surfactant, e.g., LABRASOL®, GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01), or a poloxamer, e.g., P188 or P407. In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 40 wt% amorphous vamorolone, from about 0.001 wt% to about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 60 wt% to about 90 wt% polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (e.g., SOLUPLUS®), and from about 1 wt% to about 10 wt% of a surfactant, e.g., LABRASOL®, GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01), or a poloxamer, e.g., P188 or P407. [0269] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone, from about 10 wt% to about 80 wt% methacrylic acid-methyl methacrylate copolymer (1:1) (e.g., EUDRAGIT® L100-55), optionally from about 0.1 wt% to about 10 wt% of a plasticizer, e.g., triethyl citrate and/or polyethylene glycol (e.g., PEG 400), optionally from about 0.1 wt% to about 5 wt% of a surfactant, e.g., sodium lauryl sulfate, poloxamer (e.g., poloxamer 188), and/or polysorbate 80. [0270] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone, from about 10 wt% to about 80 wt% methacrylic acid-methyl methacrylate copolymer (1:1) (e.g., EUDRAGIT® L100), optionally from about 0.1 wt% to about 10 wt% of a plasticizer, e.g., triethyl citrate and/or polyethylene glycol (e.g., PEG 400), optionally from about 0.1 wt% to about 5 wt% of a surfactant, e.g., sodium lauryl sulfate, poloxamer (e.g., poloxamer 188), and/or polysorbate 80. [0271] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 40 wt% amorphous vamorolone, from about 0.001 wt% to about 20 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 10 wt% to about 80 wt% methacrylic acid-methyl methacrylate copolymer (1:1) (e.g., EUDRAGIT® E
PO), and from about 1 wt% to about 10 wt % of a solubilizer, e.g., stearic acid. In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 40 wt% amorphous vamorolone, from about 10 wt% to about 80 wt% methacrylic acid- methyl methacrylate copolymer (1:1) (e.g., EUDRAGIT® E PO), and from about 1 wt% to about 10 wt % of a solubilizer, e.g., stearic acid. [0272] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone and from about 10 wt% to about 80 wt% poly(ethylene glycol) (e.g., PEG 3000, PEG 6000, or PEG 8000). In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone and from about 10 wt% to about 80 wt% tocopherol polyethylene glycol succinate. In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone and from about 10 wt% to about 80 wt% povidone (e.g., K-30). In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone and from about 10 wt% to about 80 wt% copovidone (e.g., KOLLIDON® VA64). In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone and from about 10 wt% to about 80 wt% hydroxypropyl cellulose (e.g., KLUCEL™ ELF). [0273] In some aspects, the amorphous solid dispersion can comprise from about 10 wt% to about 80 wt% amorphous vamorolone, from about 10 wt% to about 80 wt% poly(ethylene glycol) (e.g., PEG 3000, PEG 6000, or PEG 8000), and optionally from about 10 wt% to about 80 wt% of a filler, e.g., microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, starch, pregelatinized starch, and/or dicalcium phosphate. Drug-Layered Particles [0274] In certain embodiments, the present disclosure also provides a pharmaceutical composition comprising: a) a plurality of coated particles, wherein each coated particle comprises: i) an inert core; ii) a first drug layer coated over the inert core, the first drug layer comprising amorphous vamorolone and a first polymer; and
iii) a first encapsulation layer coated over the first drug layer, the first encapsulation layer comprising a second polymer; and b) optionally one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is a solid oral dosage form. [0275] In some aspects, the inert core can be a microcrystalline cellulose sphere, a sugar sphere, a silica sphere, dicalcium phosphate anhydrous, magnesium alumino-metasilicate, microcrystalline cellulose, or a combination of any of the foregoing. [0276] In some aspects, the first drug layer can comprise from about 15 wt% to about 95 wt% amorphous vamorolone relative to the total mass of the coated particle. In some aspects, the first drug layer can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone relative to the total mass of the coated particle. [0277] In some aspects, the first drug layer can comprise about 80 wt% amorphous vamorolone relative to the total mass of the coated particle. In some aspects, the first drug layer can comprise about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% amorphous vamorolone relative to the total mass of the coated particle.
[0278] In some aspects, the first drug layer can comprise from about 0.1 wt% to about 95 wt% amorphous vamorolone relative to the total mass of the pharmaceutical composition. In some aspects, the first drug layer can comprise from about 0.01 wt% to about 0.1 wt%, from about 0.01 wt% to about 0.5 wt%, from about 0.01 wt% to about 1 wt%, from about 0.01 wt% to about 10 wt%, from about 0.01 wt% to about 25 wt%, from about 0.01 wt% to about 50 wt%, from about 0.01 wt% to about 75 wt%, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 25 wt%, from about 0.1 wt% to about 50 wt%, from about 0.1 wt% to about 75 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 10 wt%, from about 0.5 wt% to about 25 wt%, from about 0.5 wt% to about 50 wt%, from about 0.5 wt% to about 75 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 25 wt%, from about 1 wt% to about 50 wt%, from about 1 wt% to about 75 wt%, from about 10 wt% to about 25 wt%, from about 10 wt% to about 50 wt%, from about 10 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone relative to the total mass of the pharmaceutical composition. [0279] In some aspects, the first drug layer can comprise about 80 wt% amorphous vamorolone relative to the total mass of the pharmaceutical composition. In some aspects, the first drug layer can comprise about 15 wt%, about 20 wt%, about 25 wt%, about 30
wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% amorphous vamorolone relative to the total mass of the pharmaceutical composition. [0280] In some aspects, the inert core can comprise from about 5 wt% to about 90 wt% of a total mass of the coated particle. In some aspects, the inert core can comprise from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 5 wt% to about 85 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 15 wt% to about 90 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 90 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 90 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 90 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 90 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 90 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 90 wt%, or from about 85 wt% to about 90 wt% of the total mass of the coated particle. [0281] In some aspects, the inert core can comprise about 80 wt% of the total mass of the coated particle. In some aspects, the inert core can comprise about 5 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 85 wt%, or about 90 wt% of the total mass of the coated particle.
[0282] In some aspects, the first drug layer can comprise from about 15 wt% to about 95 wt% amorphous vamorolone and the inert core can comprise from about 5 wt% to about 90 wt% of the total mass of the coated particle. [0283] In some aspects, the first polymer can comprise hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing. [0284] In some aspects, the first drug layer can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone relative to the total mass of the coated particle and from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95
wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% of the first polymer relative to the total mass of the coated particle, wherein the first polymer can comprise hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing. [0285] In some aspects, the first drug layer can comprise from about 30 wt% to about 80 wt% of the total mass of the coated particle. In some aspects, the first drug layer can comprise from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, or from about 70 wt% to about 80 wt% of the total mass of the coated particle. [0286] In some aspects, the first drug layer can comprise about 50 wt% of the total mass of the coated particle. In some aspects, the first drug layer can comprise about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, or about 80 wt% of the total mass of the coated particle. [0287] In some aspects, the first drug layer can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, the inert core can comprise from about 5 wt% to about 90 wt% of a total mass of the coated particle, and the first drug layer can comprise from about 30 wt% to about 80 wt% of the total mass of the coated particle. [0288] In some aspects, the second polymer can comprise hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer
(SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing. [0289] In some aspects, the first polymer and the second polymer can be the same. In some aspects, the first polymer and the second polymer can be different. [0290] In some aspects, the first encapsulation layer can comprises from about 30 wt% to about 80 wt % of the total mass of the coated particle. [0291] In some aspects, the first encapsulation layer can comprise from about 30 wt% to about 80 wt% of the total mass of the coated particle. In some aspects, the first encapsulation layer can comprise from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, or from about 70 wt% to about 80 wt% of the total mass of the coated particle. [0292] In some aspects, the first encapsulation layer can comprise about 50 wt% of the total mass of the coated particle. In some aspects, the first encapsulation layer can comprise about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, or about 80 wt% of the total mass of the coated particle. [0293] In some aspects, the first drug layer can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95
wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone relative to the total mass of the coated particle, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% of the first polymer relative to the total mass of the coated particle, wherein the first polymer can comprise hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing, and from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from
about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% of the second polymer relative to the total mass of the coated particle, wherein the second polymer can comprise hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing. [0294] In some aspects, the first drug layer can comprise from about 15 wt% to about 95 wt% amorphous vamorolone, the inert core can comprise from about 5 wt% to about 90 wt% of a total mass of the coated particle, the first drug layer can comprise from about 30 wt% to about 80 wt% of the total mass of the coated particle, and the first encapsulation layer can comprise from about 30 wt% to about 80 wt% of the total mass of the coated particle. [0295] In some aspects, the plurality of coated particles can further comprise additional drug layers, i.e., a second drug layer, a third drug layer, a fourth drug layer, etc., and/or additional encapsulation layers, i.e., a second encapsulation layer, a third encapsulation layer, a fourth encapsulation layer, etc. These layers can have any of compositions described above for the first drug layer and first encapsulation layer, respectively. [0296] In some aspects, the inert core can be a microcrystalline cellulose sphere, the inert core can comprise from about 10 wt% to about 80 wt% of a total mass of the coated particle and the first drug layer can comprise from about 10 wt% to about 60 wt% amorphous vamorolone and from about 10 wt% to about 80 wt% of the first polymer, e.g., HPMCAS, HPMC, HPC, povidone, copovidone, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), or methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L100). [0297] In some aspects, the inert core can be a microcrystalline cellulose sphere, a sugar sphere, a silica sphere, dicalcium phosphate anhydrous, magnesium alumino-metasilicate, microcrystalline cellulose, or a combination of any of the foregoing, the inert core can comprise from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from
about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 5 wt% to about 85 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 15 wt% to about 90 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 90 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 90 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 90 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 90 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 90 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 90 wt%, or from about 85 wt% to about 90 wt% of the total mass of the coated particle, the first drug layer can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt%
to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone relative to the total mass of the coated particle and from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% of the first polymer relative to the total mass of the coated particle, wherein the first polymer can comprise hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing, and the first encapsulation layer can comprise from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, or from about 70 wt% to about 80 wt% of the total mass of the coated particle, wherein the first encapsulation layer can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt%
to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% of the second polymer relative to the total mass of the coated particle, wherein the second polymer can comprise hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing,. [0298] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the coated particles, optionally one or more diluents having a wt% as described below, optionally one or more disintegrants having a wt% as described below, optionally one or more lubricants having a wt% as described below, optionally one or more flow enhancers having a wt% as described below, optionally one or more suspending agents having a wt% as described below, optionally one or more buffering agents having a wt% as described below, optionally one or more wetting agents having a wt% as described below, optionally one or more preservatives having a wt% as described below, optionally one or more flavoring agents having a wt% as described below, and optionally one or more flow enhancers having a wt% as described below. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 20 wt% to about 90 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt%
to about 90 wt%, from about 30 wt% to about 95 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 90 wt%, from about 40 wt% to about 95 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 90 wt%, from about 50 wt% to about 95 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 90 wt%, from about 60 wt% to about 95 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 90 wt%, from about 70 wt% to about 95 wt%, from about 80 wt% to about 90 wt%, from about 80 wt% to about 95 wt%, or from about 90 wt% to about 95 wt% of the coated particles. [0299] In some aspects, the pharmaceutical composition can comprise about 80 wt% of the coated particle. In some aspects, the pharmaceutical composition can comprise about 5 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 85 wt%, about 90 wt%, or about 95 wt% of the coated particles. [0300] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 20 wt% to about 90 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 90 wt%, from about 30 wt% to about 95 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 90 wt%, from about 40 wt% to about 95 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 90 wt%, from about 50 wt% to about 95 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 90 wt%, from about 60 wt% to about 95 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 90 wt%, from about 70 wt% to about 95 wt%, from about 80 wt% to about 90 wt%, from about 80 wt% to about 95 wt%, or from about 90 wt% to about 95 wt% of the coated particles, and from about 5 wt% to about 15 wt%, about 5 wt% to about 25 wt%, about 5
wt% to about 35 wt%, about 5 wt% to about 45 wt%, about 5 wt% to about 55 wt%, about 5 wt% to about 65 wt%, about 5 wt% to about 75 wt%, about 15 wt% to about 25 wt%, about 15 wt% to about 35 wt%, about 15 wt% to about 45 wt%, about 15 wt% to about 55 wt%, about 15 wt% to about 65 wt%, about 15 wt% to about 75 wt%, about 15 wt% to about 85 wt%, about 25 wt% to about 35 wt%, about 25 wt% to about 45 wt%, about 25 wt% to about 55 wt%, about 25 wt% to about 65 wt%, about 25 wt% to about 75 wt%, about 25 wt% to about 85 wt%, about 35 wt% to about 45 wt%, about 35 wt% to about 55 wt%, about 35 wt% to about 65 wt%, about 35 wt% to about 75 wt%, about 35 wt% to about 85 wt%, about 45 wt% to about 55 wt%, about 45 wt% to about 65 wt%, about 45 wt% to about 75 wt%, about 45 wt% to about 85 wt%, about 55 wt% to about 65 wt%, about 55 wt% to about 75 wt%, about 55 wt% to about 85 wt%, about 65 wt% to about 75 wt%, about 65 wt% to about 85 wt%, or about 75 wt% to about 85 wt% of one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, sucrose, starch, pregelatinized starch (partially or fully gelatinized), dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate, maltodextrin, or a combination of any of the foregoing. [0301] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 20 wt% to about 90 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 90 wt%, from about 30 wt% to about 95 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 90 wt%, from about 40 wt% to about 95 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 90 wt%, from about 50 wt% to about 95 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 90 wt%, from about 60 wt% to about 95 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 90 wt%, from about 70 wt% to about 95 wt%, from about 80 wt% to about 90 wt%, from about 80 wt% to about 95 wt%, or from about 90 wt% to about 95 wt% of the coated
particles, from about 5 wt% to about 15 wt%, about 5 wt% to about 25 wt%, about 5 wt% to about 35 wt%, about 5 wt% to about 45 wt%, about 5 wt% to about 55 wt%, about 5 wt% to about 65 wt%, about 5 wt% to about 75 wt%, about 15 wt% to about 25 wt%, about 15 wt% to about 35 wt%, about 15 wt% to about 45 wt%, about 15 wt% to about 55 wt%, about 15 wt% to about 65 wt%, about 15 wt% to about 75 wt%, about 15 wt% to about 85 wt%, about 25 wt% to about 35 wt%, about 25 wt% to about 45 wt%, about 25 wt% to about 55 wt%, about 25 wt% to about 65 wt%, about 25 wt% to about 75 wt%, about 25 wt% to about 85 wt%, about 35 wt% to about 45 wt%, about 35 wt% to about 55 wt%, about 35 wt% to about 65 wt%, about 35 wt% to about 75 wt%, about 35 wt% to about 85 wt%, about 45 wt% to about 55 wt%, about 45 wt% to about 65 wt%, about 45 wt% to about 75 wt%, about 45 wt% to about 85 wt%, about 55 wt% to about 65 wt%, about 55 wt% to about 75 wt%, about 55 wt% to about 85 wt%, about 65 wt% to about 75 wt%, about 65 wt% to about 85 wt%, or about 75 wt% to about 85 wt% of one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, sucrose, starch, pregelatinized starch (partially or fully gelatinized), dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate, maltodextrin, or a combination of any of the foregoing, and from about 0.25 wt% to about 0.5 wt%, from about 0.25 wt% to about 1 wt%, from about 0.25 wt% to about 2.5 wt%, from about 0.25 wt% to about 5 wt%, from about 0.25 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of one or more disintegrants, wherein the one or more disintegrants can comprise croscarmellose sodium, carmellose sodium, sodium starch glycolate (e.g., type A or B), carboxymethylcellulose sodium, carboxymethylcellulose calcium, crospovidone, starch, microcrystalline cellulose, low- substituted hydroxypropyl cellulose (e.g., LH-21), or a combination of any of the foregoing.
[0302] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 20 wt% to about 90 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 90 wt%, from about 30 wt% to about 95 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 90 wt%, from about 40 wt% to about 95 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 90 wt%, from about 50 wt% to about 95 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 90 wt%, from about 60 wt% to about 95 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 90 wt%, from about 70 wt% to about 95 wt%, from about 80 wt% to about 90 wt%, from about 80 wt% to about 95 wt%, or from about 90 wt% to about 95 wt% of the coated particles, from about 5 wt% to about 15 wt%, about 5 wt% to about 25 wt%, about 5 wt% to about 35 wt%, about 5 wt% to about 45 wt%, about 5 wt% to about 55 wt%, about 5 wt% to about 65 wt%, about 5 wt% to about 75 wt%, about 15 wt% to about 25 wt%, about 15 wt% to about 35 wt%, about 15 wt% to about 45 wt%, about 15 wt% to about 55 wt%, about 15 wt% to about 65 wt%, about 15 wt% to about 75 wt%, about 15 wt% to about 85 wt%, about 25 wt% to about 35 wt%, about 25 wt% to about 45 wt%, about 25 wt% to about 55 wt%, about 25 wt% to about 65 wt%, about 25 wt% to about 75 wt%, about 25 wt% to about 85 wt%, about 35 wt% to about 45 wt%, about 35 wt% to about 55 wt%, about 35 wt% to about 65 wt%, about 35 wt% to about 75 wt%, about 35 wt% to about 85 wt%, about 45 wt% to about 55 wt%, about 45 wt% to about 65 wt%, about 45 wt% to about 75 wt%, about 45 wt% to about 85 wt%, about 55 wt% to about 65 wt%, about 55 wt% to about 75 wt%, about 55 wt% to about 85 wt%, about 65 wt% to about 75 wt%, about 65 wt% to about 85 wt%, or about 75 wt% to about 85 wt% of one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, sucrose, starch, pregelatinized starch (partially or fully gelatinized), dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed
dicalcium phosphate, maltodextrin, or a combination of any of the foregoing, from about 0.25 wt% to about 0.5 wt%, from about 0.25 wt% to about 1 wt%, from about 0.25 wt% to about 2.5 wt%, from about 0.25 wt% to about 5 wt%, from about 0.25 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of one or more disintegrants, wherein the one or more disintegrants can comprise croscarmellose sodium, carmellose sodium, sodium starch glycolate (e.g., type A or B), carboxymethylcellulose sodium, carboxymethylcellulose calcium, crospovidone, starch, microcrystalline cellulose, low- substituted hydroxypropyl cellulose (e.g., LH-21), or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of one or more lubricants, wherein the one or more lubricants can comprise magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing. [0303] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 20 wt% to about 90 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 90 wt%, from about 30 wt% to about 95 wt%, from about 40 wt%
to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 90 wt%, from about 40 wt% to about 95 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 90 wt%, from about 50 wt% to about 95 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 90 wt%, from about 60 wt% to about 95 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 90 wt%, from about 70 wt% to about 95 wt%, from about 80 wt% to about 90 wt%, from about 80 wt% to about 95 wt%, or from about 90 wt% to about 95 wt% of the coated particles, from about 5 wt% to about 15 wt%, about 5 wt% to about 25 wt%, about 5 wt% to about 35 wt%, about 5 wt% to about 45 wt%, about 5 wt% to about 55 wt%, about 5 wt% to about 65 wt%, about 5 wt% to about 75 wt%, about 15 wt% to about 25 wt%, about 15 wt% to about 35 wt%, about 15 wt% to about 45 wt%, about 15 wt% to about 55 wt%, about 15 wt% to about 65 wt%, about 15 wt% to about 75 wt%, about 15 wt% to about 85 wt%, about 25 wt% to about 35 wt%, about 25 wt% to about 45 wt%, about 25 wt% to about 55 wt%, about 25 wt% to about 65 wt%, about 25 wt% to about 75 wt%, about 25 wt% to about 85 wt%, about 35 wt% to about 45 wt%, about 35 wt% to about 55 wt%, about 35 wt% to about 65 wt%, about 35 wt% to about 75 wt%, about 35 wt% to about 85 wt%, about 45 wt% to about 55 wt%, about 45 wt% to about 65 wt%, about 45 wt% to about 75 wt%, about 45 wt% to about 85 wt%, about 55 wt% to about 65 wt%, about 55 wt% to about 75 wt%, about 55 wt% to about 85 wt%, about 65 wt% to about 75 wt%, about 65 wt% to about 85 wt%, or about 75 wt% to about 85 wt% of one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, sucrose, starch, pregelatinized starch (partially or fully gelatinized), dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate, maltodextrin, or a combination of any of the foregoing, from about 0.25 wt% to about 0.5 wt%, from about 0.25 wt% to about 1 wt%, from about 0.25 wt% to about 2.5 wt%, from about 0.25 wt% to about 5 wt%, from about 0.25 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%,
from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of one or more disintegrants, wherein the one or more disintegrants can comprise croscarmellose sodium, carmellose sodium, sodium starch glycolate (e.g., type A or B), carboxymethylcellulose sodium, carboxymethylcellulose calcium, crospovidone, starch, microcrystalline cellulose, low- substituted hydroxypropyl cellulose (e.g., LH-21), or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of one or more lubricants, wherein the one or more lubricants can comprise magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of one or more flow enhancers, wherein the one or more flow enhancers can comprise magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing. [0304] In some aspects, the pharmaceutical composition can be prepared by fluid bed drug layering.
[0305] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the plurality of coated particles and optionally from about 5 wt% to about 85 wt% of one or more diluents. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the plurality of coated particles, optionally from about 5 wt% to about 85 wt% of one or more diluents, and optionally from about 0.25 wt% to about 10 wt% of one or more disintegrants. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the plurality of coated particles, optionally from about 5 wt% to about 85 wt% of one or more diluents, optionally from about 0.25 wt% to about 10 wt% of one or more disintegrants, and optionally from about 0.1 wt% to about 5 wt% of one or more lubricants. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the plurality of coated particles, optionally from about 5 wt% to about 85 wt% of one or more diluents, optionally from about 0.25 wt% to about 10 wt% of one or more disintegrants, optionally from about 0.1 wt% to about 5 wt% of one or more lubricants, and optionally from about 0.1 wt% to about 5 wt% of one or more flow enhancers. [0306] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the plurality of coated particles and optionally from about 5 wt% to about 80 wt% of one or more suspending agents. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the plurality of coated particles, optionally from about 5 wt% to about 80 wt% of one or more suspending agents, and optionally from about 0.1 wt% to about 5 wt% of one or more buffering agents. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the plurality of coated particles, optionally from about 5 wt% to about 80 wt% of one or more suspending agents, optionally from about 0.1 wt% to about 5 wt% of one or more buffering agents, and optionally from about 0.1 wt% to about 10 wt% of one or more wetting agents. In some aspects, the pharmaceutical composition comp can comprise from about 20 wt% to about 95 wt% of the plurality of coated particles, optionally from about 5 wt% to about 80 wt% of one or more suspending agents, optionally from about 0.1 wt% to about 5 wt% of one or more buffering agents, optionally from about 0.1 wt% to about 10 wt% of one or more wetting agents, and optionally from about 0.1 wt% to about 5 wt% of one or more preservatives. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95
wt% of the plurality of coated particles, optionally from about 5 wt% to about 80 wt% of one or more suspending agents, optionally from about 0.1 wt% to about 5 wt% of one or more buffering agents, optionally from about 0.1 wt% to about 10 wt% of one or more wetting agents, optionally from about 0.1 wt% to about 5 wt% of one or more preservatives, and from about 0.1 wt% to about 5 wt% of one or more flavoring agents. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 95 wt% of the plurality of coated particles, optionally from about 5 wt% to about 80 wt% of one or more suspending agents, optionally from about 0.1 wt% to about 5 wt% of one or more buffering agents, optionally from about 0.1 wt% to about 10 wt% of one or more wetting agents, optionally from about 0.1 wt% to about 5 wt% of one or more preservatives, from about 0.1 wt% to about 5 wt% of one or more flavoring agents, and from about 0.1 wt% to about 5 wt% of one or more flow enhancers. [0307] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 20 wt% to about 90 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 90 wt%, from about 30 wt% to about 95 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 90 wt%, from about 40 wt% to about 95 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 90 wt%, from about 50 wt% to about 95 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 90 wt%, from about 60 wt% to about 95 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 90 wt%, from about 70 wt% to about 95 wt%, from about 80 wt% to about 90 wt%, from about 80 wt% to about 95 wt%, or from about 90 wt% to about 95 wt% of the coated particles and from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt%
to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 80 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 80 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 80 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 80 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 80 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 80 wt%, or from about 75 wt% to about 80 wt% of one or more suspending agents, wherein the one or more suspending agents can comprise hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing. [0308] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 20 wt% to about 90 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 90 wt%, from about 30 wt% to about 95 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 90 wt%, from about 40 wt% to about 95 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 90 wt%, from about 50 wt% to about 95 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 90 wt%, from about 60 wt% to about 95 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 90 wt%, from about 70 wt% to about 95 wt%, from about 80 wt% to about 90 wt%, from about 80 wt% to about 95 wt%, or from about 90 wt% to about 95 wt% of the coated particles, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%,
from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 80 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 80 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 80 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 80 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 80 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 80 wt%, or from about 75 wt% to about 80 wt% of one or more suspending agents, wherein the one or more suspending agents can comprise hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of one or more buffering agents, wherein the one or more buffering agents can comprise a citrate buffer, a phosphate buffer, a carbonate buffer, or a combination of any of the foregoing. [0309] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 20 wt% to about 90 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 90 wt%, from about 30 wt% to about 95 wt%, from about 40 wt%
to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 90 wt%, from about 40 wt% to about 95 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 90 wt%, from about 50 wt% to about 95 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 90 wt%, from about 60 wt% to about 95 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 90 wt%, from about 70 wt% to about 95 wt%, from about 80 wt% to about 90 wt%, from about 80 wt% to about 95 wt%, or from about 90 wt% to about 95 wt% of the coated particles, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 80 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 80 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 80 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 80 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 80 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 80 wt%, or from about 75 wt% to about 80 wt% of one or more suspending agents, wherein the one or more suspending agents can comprise hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1
wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of one or more buffering agents, wherein the one or more buffering agents can comprise a citrate buffer, a phosphate buffer, a carbonate buffer, or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of one or more wetting agents, wherein the one or more wetting agents can comprise sodium lauryl sulfate, a poloxamer, a polysorbate, or a combination of any of the foregoing. [0310] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 20 wt% to about 90 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 90 wt%, from about 30 wt% to about 95 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 90 wt%, from about 40 wt% to about 95 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 90 wt%, from about 50 wt% to about 95 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 90 wt%, from about 60 wt% to about 95 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 90 wt%, from about 70 wt% to about 95 wt%, from about 80 wt% to about 90 wt%, from about 80 wt% to about 95 wt%, or from about 90 wt% to about 95 wt% of the coated particles, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from
about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 80 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 80 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 80 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 80 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 80 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 80 wt%, or from about 75 wt% to about 80 wt% of one or more suspending agents, wherein the one or more suspending agents can comprise hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of one or more buffering agents, wherein the one or more buffering agents can comprise a citrate buffer, a phosphate buffer, a carbonate buffer, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to
about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of one or more wetting agents, wherein the one or more wetting agents can comprise sodium lauryl sulfate, a poloxamer, a polysorbate, or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of one or more preservatives, wherein the one or more preservatives can comprise methyl paraben, propyl paraben, sodium benzoate, citric acid, ascorbic acid, or a combination of any of the foregoing. [0311] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 20 wt% to about 90 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 90 wt%, from about 30 wt% to about 95 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 90 wt%, from about 40 wt% to about 95 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 90 wt%, from about 50 wt% to about 95 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 90 wt%, from about 60 wt% to about 95 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 90 wt%, from about 70 wt% to about 95 wt%, from about 80 wt% to about 90 wt%, from about 80 wt% to about 95 wt%, or from about 90 wt% to about 95 wt% of the coated
particles, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 80 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 80 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 80 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 80 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 80 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 80 wt%, or from about 75 wt% to about 80 wt% of one or more suspending agents, wherein the one or more suspending agents can comprise hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of one or more buffering agents, wherein the one or more buffering agents can comprise a citrate buffer, a phosphate buffer, a carbonate buffer, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about
0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of one or more wetting agents, wherein the one or more wetting agents can comprise sodium lauryl sulfate, a poloxamer, a polysorbate, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of one or more preservatives, wherein the one or more preservatives can comprise methyl paraben, propyl paraben, sodium benzoate, citric acid, ascorbic acid, or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of one or more flavoring agents, wherein the one or more flavoring agents can comprise sucrose, aspartame, an artificial flavor (e.g, peppermint, bubblegum, or grape), a natural flavor, or a combination of any of the foregoing. [0312] The present disclosure also provides pharmaceutical compositions comprising: a) a plurality of coated particles, wherein each coated particle comprises: i) a core comprising amorphous vamorolone and a first polymer; and
ii) a first encapsulation layer coated over the core, the first encapsulation layer comprising a second polymer; and b) optionally one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is a solid oral dosage form. [0313] In some aspects, the core comprising amorphous vamorolone and a first polymer can be an amorphous solid dispersion in the form of a granule or pellet, e.g., one of the amorphous solid dispersions described above. In some aspects, the core comprising amorphous vamorolone and a first polymer can be an amorphous solid dispersion in the form of a granule or pellet comprising from about 15 wt% to about 95 wt% amorphous vamorolone, from about 5 wt% to about 85 wt% of the first polymer, optionally from about 0.1 wt% to about 25 wt% of a plasticizer, optionally from about 0.1 wt% to about 10 wt% of a surfactant, optionally from about 1 wt% to about 40 wt% of a solubilizing agent, and optionally from about 10 wt% to about 80 wt% of a filler. [0314] In some aspects, the core comprising amorphous vamorolone and a first polymer can be an amorphous solid dispersion in the form of a granule or pellet comprising from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone and from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5
wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the first polymer, wherein the first polymer can comprise hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate- polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing. [0315] In some aspects, the core comprising amorphous vamorolone and a first polymer can be an amorphous solid dispersion in the form of a granule or pellet comprising from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt%
to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the first polymer, wherein the first polymer can comprise hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing, and from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 25 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 25 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 25 wt%, from about 15 wt% to about 20 wt%, from about 15 wt% to about 25 wt%, or from about 20 wt% to about 25 wt% of a plasticizer, wherein the plasticizer can comprise a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g.,
diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing. [0316] In some aspects, the core comprising amorphous vamorolone and a first polymer can be an amorphous solid dispersion in the form of a granule or pellet comprising from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75
wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the first polymer, wherein the first polymer can comprise hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 25 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 25 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 25 wt%, from about 15 wt% to about 20 wt%, from about 15 wt% to about 25 wt%, or from about 20 wt% to about 25 wt% of a plasticizer, wherein the plasticizer can comprise a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of a surfactant, wherein the surfactant can comprise sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a
polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing. [0317] In some aspects, the core comprising amorphous vamorolone and a first polymer can be an amorphous solid dispersion in the form of a granule or pellet comprising from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75
wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the first polymer, wherein the first polymer can comprise hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 25 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 25 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 25 wt%, from about 15 wt% to about 20 wt%, from about 15 wt% to about 25 wt%, or from about 20 wt% to about 25 wt% of a plasticizer, wherein the plasticizer can comprise a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of a surfactant, wherein the surfactant can comprise sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a
polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing, and from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 30 wt%, %, from about 5 wt% to about 10 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 40 wt%,%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%,%, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, or from about 30 wt% to about 40 wt% of a solubilizing agent, such as a cyclodextrin. [0318] In some aspects, the core comprising amorphous vamorolone and a first polymer can be an amorphous solid dispersion in the form of a granule or pellet comprising from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone, from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15
wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of the first polymer, wherein the first polymer can comprise hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone, caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or a combination of any of the foregoing, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.1 wt% to about 15 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 15 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 25 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 25 wt%, from about 10 wt% to about 15 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 25 wt%, from about 15 wt% to about 20 wt%, from about 15 wt% to about 25 wt%, or from about 20 wt% to about 25 wt% of a plasticizer, wherein the plasticizer can comprise a citrate ester, e.g., triethyl citrate, tributyl citrate, acetyl triethyl citrate, or acetyl tributyl citrate; a fatty acid ester, e.g., butyl stearate, glycerol monostearate, or stearyl alcohol; a phthalate ester, e.g., diethyl phthalate or dibutyl phthalate; poly(ethylene glycol), e.g., having a molecular weight of from about 400 to about 3,500; poly(propylene glycol); tocopherol polyethylene glycol succinate; dibutyl sebacate; triacetin; a polysorbate; a sugar alcohol, e.g., sorbitol, xylitol, lactitol, or erythriol; or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%,
from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of a surfactant, wherein the surfactant can comprise sodium lauryl sulfate; a poloxamer, e.g., P188 or P407; a polysorbate, e.g., T80; tocopherol polyethylene glycol succinate; poly(ethylene glycol), e.g., having a molecular weight of from about 3,350 to about 8,000; a fatty acid triglyceride, e.g., LABRASOL® or GELUCIRE® (e.g., grade 48/16, 59/14, 50/13, 44/14, or 43/01); or a combination of any of the foregoing, optionally from about 1 wt% to about 5 wt%, from about 1 wt% to about 10 wt%, from about 1 wt% to about 20 wt%, from about 1 wt% to about 30 wt%, %, from about 5 wt% to about 10 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 40 wt%,%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%,%, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, or from about 30 wt% to about 40 wt% of a solubilizing agent, such as a cyclodextrin, and from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%, from about 10 wt% to about 50 wt%, from about 10 wt% to about 60 wt%, from about 10 wt% to about 70 wt%, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 30 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, or from about 70 wt% to about 80 wt% of a filler, wherein the filler can comprise microcrystalline cellulose (e.g., standard (PH grades), fibrous (KG grades), or mixed (UF grades)), silicified microcrystalline cellulose, carboxymethylcellulose sodium, methylcellulose, hydroxyethylmethyl cellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl
cellulose, povidone, copovidone, lactose monohydrate, lactose anhydrous, mannitol, sucrose, dextrates (EMDEX® or CAMDEX®), maltodextrin, polydextrose, starch, pregelatinized starch (partially or fully gelatinized), hydroxypropyl starch, carbomer, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate and maltodextrin, polycarbophil, or a combination of any of the foregoing. Tablet or Capsule Solid Oral Dosage Forms [0319] In some aspects, the solid oral dosage forms described above can be a tablet or a capsule. For example, the amorphous solid dispersions or coated particles described above can be blended with one or more pharmaceutical excipients, e.g., excipients appropriate for a tablet or capsule solid oral dosage form, and then can be compressed into a table or filled into, for example, a hard or soft gelatin capsule. [0320] In some aspects, the one or more pharmaceutically acceptable excipients can comprise one or more diluents, one or more disintegrants, one or more lubricants, one or more flow enhancers, or a combination of any of the foregoing. [0321] In some aspects, the one or more pharmaceutically acceptable excipients can comprise one or more diluents. In some aspects, the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, sucrose, starch, pregelatinized starch (partially or fully gelatinized), dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate, maltodextrin, or a combination of any of the foregoing. [0322] In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 85 wt% of the one or more diluents. In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 15 wt%, about 5 wt% to about 25 wt%, about 5 wt% to about 35 wt%, about 5 wt% to about 45 wt%, about 5 wt% to about 55 wt%, about 5 wt% to about 65 wt%, about 5 wt% to about 75 wt%, about 15 wt% to about 25 wt%, about 15 wt% to about 35 wt%, about 15 wt% to about 45 wt%, about 15 wt% to about 55 wt%, about 15 wt% to about 65 wt%, about 15 wt% to about 75 wt%, about 15 wt% to about 85 wt%, about 25 wt% to about 35 wt%, about 25 wt% to about 45 wt%, about 25 wt% to about 55 wt%, about 25 wt% to about 65 wt%, about 25 wt% to about 75 wt%, about 25 wt% to about 85 wt%, about 35 wt% to about 45 wt%, about 35
wt% to about 55 wt%, about 35 wt% to about 65 wt%, about 35 wt% to about 75 wt%, about 35 wt% to about 85 wt%, about 45 wt% to about 55 wt%, about 45 wt% to about 65 wt%, about 45 wt% to about 75 wt%, about 45 wt% to about 85 wt%, about 55 wt% to about 65 wt%, about 55 wt% to about 75 wt%, about 55 wt% to about 85 wt%, about 65 wt% to about 75 wt%, about 65 wt% to about 85 wt%, or about 75 wt% to about 85 wt% of the one or more diluents. [0323] In some aspects, the pharmaceutical composition can comprise about 20 wt% of the one or more diluents. In some aspects, the pharmaceutical composition can comprise about 5 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, or about 85 wt% of the one or more diluents. [0324] In some aspects, the one or more pharmaceutically acceptable excipients can comprise one or more disintegrants. In some aspects, the one or more disintegrants can comprise croscarmellose sodium, carmellose sodium, sodium starch glycolate (e.g., type A or B), carboxymethylcellulose sodium, carboxymethylcellulose calcium, crospovidone, starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose (e.g., LH-21), or a combination of any of the foregoing. [0325] In some aspects, the pharmaceutical composition can comprise from about 0.25 wt% to about 10 wt% of the one or more disintegrants. In some aspects, the pharmaceutical composition can comprise from about 0.25 wt% to about 0.5 wt%, from about 0.25 wt% to about 1 wt%, from about 0.25 wt% to about 2.5 wt%, from about 0.25 wt% to about 5 wt%, from about 0.25 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more disintegrants. [0326] In some aspects, the pharmaceutical composition can comprise about 5 wt% of the one or more disintegrants. In some aspects, the pharmaceutical composition can comprise about 0.25 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%,
about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt% of the one or more disintegrants. [0327] In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 15 wt%, about 5 wt% to about 25 wt%, about 5 wt% to about 35 wt%, about 5 wt% to about 45 wt%, about 5 wt% to about 55 wt%, about 5 wt% to about 65 wt%, about 5 wt% to about 75 wt%, about 15 wt% to about 25 wt%, about 15 wt% to about 35 wt%, about 15 wt% to about 45 wt%, about 15 wt% to about 55 wt%, about 15 wt% to about 65 wt%, about 15 wt% to about 75 wt%, about 15 wt% to about 85 wt%, about 25 wt% to about 35 wt%, about 25 wt% to about 45 wt%, about 25 wt% to about 55 wt%, about 25 wt% to about 65 wt%, about 25 wt% to about 75 wt%, about 25 wt% to about 85 wt%, about 35 wt% to about 45 wt%, about 35 wt% to about 55 wt%, about 35 wt% to about 65 wt%, about 35 wt% to about 75 wt%, about 35 wt% to about 85 wt%, about 45 wt% to about 55 wt%, about 45 wt% to about 65 wt%, about 45 wt% to about 75 wt%, about 45 wt% to about 85 wt%, about 55 wt% to about 65 wt%, about 55 wt% to about 75 wt%, about 55 wt% to about 85 wt%, about 65 wt% to about 75 wt%, about 65 wt% to about 85 wt%, or about 75 wt% to about 85 wt% of the one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, sucrose, starch, pregelatinized starch (partially or fully gelatinized), dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate, maltodextrin, or a combination of any of the foregoing, and from about 0.25 wt% to about 0.5 wt%, from about 0.25 wt% to about 1 wt%, from about 0.25 wt% to about 2.5 wt%, from about 0.25 wt% to about 5 wt%, from about 0.25 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more disintegrants, wherein the one or more disintegrants can comprise croscarmellose sodium, carmellose sodium, sodium starch glycolate (e.g., type A or B), carboxymethylcellulose sodium, carboxymethylcellulose calcium, crospovidone, starch, microcrystalline cellulose, low-
substituted hydroxypropyl cellulose (e.g., LH-21), or a combination of any of the foregoing. [0328] In some aspects, the pharmaceutical composition can comprise one or more lubricants. In some aspects, the one or more lubricants can comprise magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing. [0329] In some aspects, the pharmaceutical composition can comprise from about 0.1 wt% to about 5 wt% of the one or more lubricants. In some aspects, wherein the pharmaceutical composition can comprise from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more lubricants. [0330] In some aspects, the pharmaceutical composition can comprise about 3 wt% of the one or more lubricants. In some aspects, the pharmaceutical composition can comprise about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, or about 5 wt% of the one or more lubricants. [0331] In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 15 wt%, about 5 wt% to about 25 wt%, about 5 wt% to about 35 wt%, about 5 wt% to about 45 wt%, about 5 wt% to about 55 wt%, about 5 wt% to about 65 wt%, about 5 wt% to about 75 wt%, about 15 wt% to about 25 wt%, about 15 wt% to about 35 wt%, about 15 wt% to about 45 wt%, about 15 wt% to about 55 wt%, about 15 wt% to about 65 wt%, about 15 wt% to about 75 wt%, about 15 wt% to about 85 wt%, about 25 wt% to about 35 wt%, about 25 wt% to about 45 wt%, about 25 wt% to about 55 wt%, about 25 wt% to about 65 wt%, about 25 wt% to about 75 wt%, about 25 wt% to about 85 wt%, about 35 wt% to about 45 wt%, about 35 wt% to about 55 wt%, about 35 wt% to about 65 wt%, about 35 wt% to about 75 wt%, about 35 wt% to about 85 wt%, about 45 wt% to about 55 wt%, about 45 wt% to about 65 wt%, about 45 wt% to about 75 wt%,
about 45 wt% to about 85 wt%, about 55 wt% to about 65 wt%, about 55 wt% to about 75 wt%, about 55 wt% to about 85 wt%, about 65 wt% to about 75 wt%, about 65 wt% to about 85 wt%, or about 75 wt% to about 85 wt% of the one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, sucrose, starch, pregelatinized starch (partially or fully gelatinized), dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate, maltodextrin, or a combination of any of the foregoing, from about 0.25 wt% to about 0.5 wt%, from about 0.25 wt% to about 1 wt%, from about 0.25 wt% to about 2.5 wt%, from about 0.25 wt% to about 5 wt%, from about 0.25 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more disintegrants, wherein the one or more disintegrants can comprise croscarmellose sodium, carmellose sodium, sodium starch glycolate (e.g., type A or B), carboxymethylcellulose sodium, carboxymethylcellulose calcium, crospovidone, starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose (e.g., LH-21), or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more lubricants, wherein the one or more lubricants can comprise magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing.
[0332] In some aspects, the pharmaceutical composition can comprise one or more flow enhancers (also referred to as a glidant). In some aspects, the one or more flow enhancers can comprise magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing. [0333] In some aspects, the pharmaceutical composition can comprise from about 0.1 wt% to about 5 wt% of the one or more flow enhancers. In some aspects, wherein the pharmaceutical composition can comprise from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more flow enhancers. [0334] In some aspects, the pharmaceutical composition can comprise about 3 wt% of the one or more flow enhancers. In some aspects, the pharmaceutical composition can comprise about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, or about 5 wt% of the one or more flow enhancers. [0335] In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 15 wt%, about 5 wt% to about 25 wt%, about 5 wt% to about 35 wt%, about 5 wt% to about 45 wt%, about 5 wt% to about 55 wt%, about 5 wt% to about 65 wt%, about 5 wt% to about 75 wt%, about 15 wt% to about 25 wt%, about 15 wt% to about 35 wt%, about 15 wt% to about 45 wt%, about 15 wt% to about 55 wt%, about 15 wt% to about 65 wt%, about 15 wt% to about 75 wt%, about 15 wt% to about 85 wt%, about 25 wt% to about 35 wt%, about 25 wt% to about 45 wt%, about 25 wt% to about 55 wt%, about 25 wt% to about 65 wt%, about 25 wt% to about 75 wt%, about 25 wt% to about 85 wt%, about 35 wt% to about 45 wt%, about 35 wt% to about 55 wt%, about 35 wt% to about 65 wt%, about 35 wt% to about 75 wt%, about 35 wt% to about 85 wt%, about 45 wt% to about 55 wt%, about 45 wt% to about 65 wt%, about 45 wt% to about 75 wt%,
about 45 wt% to about 85 wt%, about 55 wt% to about 65 wt%, about 55 wt% to about 75 wt%, about 55 wt% to about 85 wt%, about 65 wt% to about 75 wt%, about 65 wt% to about 85 wt%, or about 75 wt% to about 85 wt% of the one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, sucrose, starch, pregelatinized starch (partially or fully gelatinized), dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate, maltodextrin, or a combination of any of the foregoing, from about 0.25 wt% to about 0.5 wt%, from about 0.25 wt% to about 1 wt%, from about 0.25 wt% to about 2.5 wt%, from about 0.25 wt% to about 5 wt%, from about 0.25 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more disintegrants, wherein the one or more disintegrants can comprise croscarmellose sodium, carmellose sodium, sodium starch glycolate (e.g., type A or B), carboxymethylcellulose sodium, carboxymethylcellulose calcium, crospovidone, starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose (e.g., LH-21), or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more lubricants, wherein the one or more lubricants can comprise magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about
2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more flow enhancers, wherein the one or more flow enhancers can comprise magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing. [0336] In some aspects wherein the solid oral dosage form is a tablet, the tablet can optionally be coated with one or more film coating materials. In some aspects, the one or more film coating materials can comprise hydroxypropyl methylcellulose, poly(vinyl acetate), hydroxypropyl cellulose, polyethylene glycol, polyvinyl alcohol, or a combination of any of the foregoing. [0337] In some aspects, the pharmaceutical composition can comprise from about 1 wt% to about 10 wt% of the one or more film coating materials. In some aspects, the pharmaceutical composition can comprise from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 6 wt%, from about 1 wt% to about 7 wt%, from about 1 wt% to about 8 wt%, from about 1 wt% to about 9 wt%, from about 1 wt% to about 10 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 2 wt% to about 6 wt%, from about 2 wt% to about 7 wt%, from about 2 wt% to about 8 wt%, from about 2 wt% to about 9 wt%, from about 2 wt% to about 10 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 6 wt%, from about 3 wt% to about 7 wt%, from about 3 wt% to about 8 wt%, from about 3 wt% to about 9 wt%, from about 3 wt% to about 10 wt%, from about 4 wt% to about 5 wt%, from about 4 wt% to about 6 wt%, from about 4 wt% to about 7 wt%, from about 4 wt% to about 8 wt%, from about 4 wt% to about 9 wt%, from about 4 wt% to about 10 wt%, from about 5 wt% to about 6 wt%, from about 5 wt% to about 7 wt%, from about 5 wt% to about 8 wt%, from about 5 wt% to about 9 wt%, from about 5 wt% to about 10 wt%, from about 6 wt% to about 7 wt%, from about 6 wt% to about 8 wt%, from about 6 wt% to about 9 wt%, from about 6 wt% to about 10
wt%, from about 7 wt% to about 8 wt%, from about 7 wt% to about 9 wt%, from about 75 wt% to about 10 wt%, from about 8 wt% to about 9 wt%, from about 8 wt% to about 10 wt%, or from about 9 wt% to about 10 wt% of the one or more film coating materials. [0338] In some aspects, the pharmaceutical composition can comprise about 1 wt% of the one or more film coating materials. In some aspects, the pharmaceutical composition can comprise about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, about 5 wt%, about 5.5 wt%, about 6 wt%, about 6.5 wt%, about 7 wt%, about 7.5 wt%, about 8 wt%, about 8.5 wt%, about 9 wt%, about 9.5 wt%, or about 10 wt% of the one or more film coating materials. [0339] In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 15 wt%, about 5 wt% to about 25 wt%, about 5 wt% to about 35 wt%, about 5 wt% to about 45 wt%, about 5 wt% to about 55 wt%, about 5 wt% to about 65 wt%, about 5 wt% to about 75 wt%, about 15 wt% to about 25 wt%, about 15 wt% to about 35 wt%, about 15 wt% to about 45 wt%, about 15 wt% to about 55 wt%, about 15 wt% to about 65 wt%, about 15 wt% to about 75 wt%, about 15 wt% to about 85 wt%, about 25 wt% to about 35 wt%, about 25 wt% to about 45 wt%, about 25 wt% to about 55 wt%, about 25 wt% to about 65 wt%, about 25 wt% to about 75 wt%, about 25 wt% to about 85 wt%, about 35 wt% to about 45 wt%, about 35 wt% to about 55 wt%, about 35 wt% to about 65 wt%, about 35 wt% to about 75 wt%, about 35 wt% to about 85 wt%, about 45 wt% to about 55 wt%, about 45 wt% to about 65 wt%, about 45 wt% to about 75 wt%, about 45 wt% to about 85 wt%, about 55 wt% to about 65 wt%, about 55 wt% to about 75 wt%, about 55 wt% to about 85 wt%, about 65 wt% to about 75 wt%, about 65 wt% to about 85 wt%, or about 75 wt% to about 85 wt% of the one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, sucrose, starch, pregelatinized starch (partially or fully gelatinized), dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate anhydrous, coprocessed dicalcium phosphate, maltodextrin, or a combination of any of the foregoing, from about 0.25 wt% to about 0.5 wt%, from about 0.25 wt% to about 1 wt%, from about 0.25 wt% to about 2.5 wt%, from about 0.25 wt% to about 5 wt%, from about 0.25 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%,
from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more disintegrants, wherein the one or more disintegrants can comprise croscarmellose sodium, carmellose sodium, sodium starch glycolate (e.g., type A or B), carboxymethylcellulose sodium, carboxymethylcellulose calcium, crospovidone, starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose (e.g., LH-21), or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more lubricants, wherein the one or more lubricants can comprise magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more flow enhancers, wherein the one or more flow enhancers can comprise magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, glyceryl dibehenate, talc, colloidal silicon dioxide, or a combination of any of the foregoing, and from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 6 wt%, from about 1 wt% to about 7 wt%, from about 1 wt% to about 8 wt%, from about 1 wt%
to about 9 wt%, from about 1 wt% to about 10 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 2 wt% to about 6 wt%, from about 2 wt% to about 7 wt%, from about 2 wt% to about 8 wt%, from about 2 wt% to about 9 wt%, from about 2 wt% to about 10 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 6 wt%, from about 3 wt% to about 7 wt%, from about 3 wt% to about 8 wt%, from about 3 wt% to about 9 wt%, from about 3 wt% to about 10 wt%, from about 4 wt% to about 5 wt%, from about 4 wt% to about 6 wt%, from about 4 wt% to about 7 wt%, from about 4 wt% to about 8 wt%, from about 4 wt% to about 9 wt%, from about 4 wt% to about 10 wt%, from about 5 wt% to about 6 wt%, from about 5 wt% to about 7 wt%, from about 5 wt% to about 8 wt%, from about 5 wt% to about 9 wt%, from about 5 wt% to about 10 wt%, from about 6 wt% to about 7 wt%, from about 6 wt% to about 8 wt%, from about 6 wt% to about 9 wt%, from about 6 wt% to about 10 wt%, from about 7 wt% to about 8 wt%, from about 7 wt% to about 9 wt%, from about 75 wt% to about 10 wt%, from about 8 wt% to about 9 wt%, from about 8 wt% to about 10 wt%, or from about 9 wt% to about 10 wt% of the one or more film coating materials, wherein the one or more film coating materials can comprise hydroxypropyl methylcellulose, poly(vinyl acetate), hydroxypropyl cellulose, polyethylene glycol, polyvinyl alcohol, or a combination of any of the foregoing. [0340] In some aspects, the pharmaceutical composition can comprise: - from about 20 wt% to about 80 wt% of any of the amorphous solid dispersions described above; - from about 5 wt% to about 60 wt% of one or more fillers, e.g., microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, starch, pregelitanized starch, and/or dicalcium phosphate; - optionally from about 0.1 wt% to about 5 wt% of one or more disintegrants, e.g., croscarmellose sodium, sodium starch glycolate, and/or crospovidone; - optionally from about 0.1 wt% to about 1 wt% of one or more flow enhancers, e.g., colloidal silicon dioxide and/or talc; - optionally from about 0.1 wt% to about 2 wt% of one or more lubricants, e.g., magnesium stearate, stearic acid, sodium stearyl fumarate, and/or glyceryl dibehenate; and
- optionally from about 2 wt% to about 8 wt% of one or more film coating materials, e.g., hydroxypropyl methylcellulose, poly(vinyl acetate), hydroxypropyl cellulose, polyethylene glycol, and/or polyvinyl alcohol. [0341] In some aspects, the pharmaceutical composition can comprise: - from about 20 wt% to about 80 wt% of an amorphous solid dispersion comprising from about 10 wt% to about 60 wt% amorphous vamorolone, from about 10 wt% to about 80 wt% of a polymer, optionally a plasticizer, optionally a surfactant, and optionally a filler; - from about 5 wt% to about 60 wt% of one or more fillers, e.g., microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, lactose anhydrous, mannitol, starch, pregelitanized starch, and/or dicalcium phosphate; - optionally from about 0.1 wt% to about 5 wt% of one or more disintegrants, e.g., croscarmellose sodium, sodium starch glycolate, and/or crospovidone; - optionally from about 0.1 wt% to about 1 wt% of one or more flow enhancers, e.g., colloidal silicon dioxide and/or talc; - optionally from about 0.1 wt% to about 2 wt% of one or more lubricants, e.g., magnesium stearate, stearic acid, sodium stearyl fumarate, and/or glyceryl dibehenate; and - optionally from about 2 wt% to about 8 wt% of one or more film coating materials, e.g., hydroxypropyl methylcellulose, poly(vinyl acetate), hydroxypropyl cellulose, polyethylene glycol, and/or polyvinyl alcohol. [0342] In some aspects, the pharmaceutical composition can comprise: - from about 20 wt% to about 80 wt% of any of the amorphous solid dispersions described above; - optionally from about 0.1 wt% to about 5 wt% of one or more disintegrants, e.g., croscarmellose sodium, sodium starch glycolate, and/or crospovidone; - optionally from about 0.1 wt% to about 1 wt% of one or more flow enhancers, e.g., colloidal silicon dioxide and/or talc; - optionally from about 0.1 wt% to about 2 wt% of one or more lubricants, e.g., magnesium stearate, stearic acid, sodium stearyl fumarate, and/or glyceryl dibehenate; and
- from about 2 wt% to about 8 wt% of one or more film coating materials, e.g., hydroxypropyl methylcellulose, poly(vinyl acetate), hydroxypropyl cellulose, polyethylene glycol, and/or polyvinyl alcohol. [0343] In some aspects, the pharmaceutical composition can comprise: - from about 20 wt% to about 80 wt% of an amorphous solid dispersion comprising from about 10 wt% to about 60 wt% amorphous vamorolone, from about 10 wt% to about 80 wt% of a polymer, optionally a plasticizer, optionally a surfactant, and optionally a filler; - optionally from about 0.1 wt% to about 5 wt% of one or more disintegrants, e.g., croscarmellose sodium, sodium starch glycolate, and/or crospovidone; - optionally from about 0.1 wt% to about 1 wt% of one or more flow enhancers, e.g., colloidal silicon dioxide and/or talc; - optionally from about 0.1 wt% to about 2 wt% of one or more lubricants, e.g., magnesium stearate, stearic acid, sodium stearyl fumarate, and/or glyceryl dibehenate; and - from about 2 wt% to about 8 wt% of one or more film coating materials, e.g., hydroxypropyl methylcellulose, poly(vinyl acetate), hydroxypropyl cellulose, polyethylene glycol, and/or polyvinyl alcohol. [0344] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 5 wt% to about 90 wt% amorphous vamorolone, from about 5 wt% to about 90 wt% of microcrystalline cellulose, from about about 5 wt% to about 90 wt% of mannitol, and from about 5 wt % to about 95 wt % lactose or lactose monohydrate; - optionally from about 0.5 wt% to about 25 wt% of a disintegrant; - optionally from about 0.1 wt% to about 10 wt% of one or more flow enhancers; and - optionally from about 0.1 wt% to about 10 wt% of one or more lubricants. [0345] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 5 wt% to about 90 wt% amorphous vamorolone, from about 5 wt% to about 90 wt% of microcrystalline cellulose, from about about 5 wt% to about 90 wt% of
mannitol, and from about 2 wt % to about 30 wt % starch or pre-gelatinized starch; - optionally from about 0.5 wt% to about 25 wt% of a disintegrant; - optionally from about 0.1 wt% to about 10 wt% of one or more flow enhancers; and - optionally from about 0.1 wt% to about 10 wt% of one or more lubricants. [0346] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 5 wt% to about 90 wt% amorphous vamorolone, from about 5 wt% to about 90 wt% of microcrystalline cellulose, from about about 5 wt% to about 90 wt% of mannitol, and from about 2 wt % to about 70 wt % sucrose or compressible sugar; - optionally from about 0.5 wt% to about 25 wt% of a disintegrant; - optionally from about 0.1 wt% to about 10 wt% of one or more flow enhancers; and - optionally from about 0.1 wt% to about 10 wt% of one or more lubricants. [0347] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 5 wt% to about 90 wt% amorphous vamorolone, from about 5 wt% to about 90 wt% of microcrystalline cellulose, from about about 5 wt% to about 90 wt% of mannitol, and from about 0.5 wt % to about 30 wt % povidone or copovidone; - optionally from about 0.5 wt% to about 25 wt% of a disintegrant; - optionally from about 0.1 wt% to about 10 wt% of one or more flow enhancers; and - optionally from about 0.1 wt% to about 10 wt% of one or more lubricants. [0348] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 5 wt% to about 90 wt% amorphous vamorolone, from about 5 wt% to about 90 wt% of microcrystalline cellulose, from about about 5 wt% to about 90 wt% of mannitol, and from about 0.5 wt % to about 50 wt % ethyl cellulose, hydroxyethyl cellulose, methyl cellulose, hydroxyethylmethyl cellulose, HPC, HPMC, hydroxypropyl starch, gelatin, or glucose; - optionally from about 0.5 wt% to about 25 wt% of a disintegrant;
- optionally from about 0.1 wt% to about 10 wt% of one or more flow enhancers; and - optionally from about 0.1 wt% to about 10 wt% of one or more lubricants. [0349] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 5 wt% to about 90 wt% amorphous vamorolone, from about 5 wt% to about 90 wt% of microcrystalline cellulose, from about about 5 wt% to about 90 wt% of mannitol, and from about 20 wt % to about 90 wt % erythritol; - optionally from about 0.5 wt% to about 25 wt% of a disintegrant; - optionally from about 0.1 wt% to about 10 wt% of one or more flow enhancers; and - optionally from about 0.1 wt% to about 10 wt% of one or more lubricants. [0350] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 5 wt% to about 90 wt% amorphous vamorolone, from about 5 wt% to about 90 wt% of microcrystalline cellulose, from about about 5 wt% to about 90 wt% of mannitol, and from about 0.5 wt % to about 60 wt % alginic acid, carbomer, carboxymethylcellulose sodium, dextrates (e.g., CAMDEX® or EMDEX®), maltodextrin, dextrin, inulin, magnesium aluminum silicate, polycarbophil, polydextrose, poly(ethylene oxide), and/or polymethacrylates; - optionally from about 0.5 wt% to about 25 wt% of a disintegrant; - optionally from about 0.1 wt% to about 10 wt% of one or more flow enhancers; and - optionally from about 0.1 wt% to about 10 wt% of one or more lubricants. [0351] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 5 wt% to about 90 wt% amorphous vamorolone, from about 5 wt% to about 90 wt% of microcrystalline cellulose, from about about 5 wt% to about 90 wt% of mannitol, and from about 1 wt % to about 60 wt % acacia, agar, ceratonia, guar gum, glyceryl behenate, vitamin E polyethylene glycol succinate, or wax (e.g., carnauba wax); - optionally from about 0.5 wt% to about 25 wt% of a disintegrant;
- optionally from about 0.1 wt% to about 10 wt% of one or more flow enhancers; and - optionally from about 0.1 wt% to about 10 wt% of one or more lubricants. [0352] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 5 wt% to about 90 wt% amorphous vamorolone, from about 5 wt% to about 90 wt% of microcrystalline cellulose, from about about 5 wt% to about 90 wt% of mannitol, and from about 1 wt % to about 50 wt % of a solubilizing agent, e.g., cyclodextrin; - optionally from about 0.5 wt% to about 25 wt% of a disintegrant; - optionally from about 0.1 wt% to about 10 wt% of one or more flow enhancers; and - optionally from about 0.1 wt% to about 10 wt% of one or more lubricants. [0353] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 10 wt% to about 70 wt% amorphous vamorolone, from about 20 wt% to about 80 wt% of microcrystalline cellulose or silicified microcrystalline cellulose, and from about about 0.5 wt% to about 10 wt% of povidone (e.g., K30) or copovidone (e.g., VA64); - from about 0.5 wt% to about 7 wt% of a disintegrant, e.g., sodium starch glycolate or crospovidone; and - from about 0.1 wt% to about 5 wt% of a lubricant, e.g., magnesium stearate and/or stearic acid. [0354] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 10 wt% to about 70 wt% amorphous vamorolone, from about 20 wt% to about 80 wt% of mannitol, and from about about 0.5 wt% to about 10 wt% of HPMC; - from about 0.5 wt% to about 7 wt% of a disintegrant, e.g., croscarmellose sodium; and - from about 0.1 wt% to about 5 wt% of a lubricant, e.g., sodium stearyl fumarate. [0355] In some aspects, the pharmaceutical composition can comprise:
- an amorphous solid dispersion comprising from about 10 wt% to about 70 wt% amorphous vamorolone, from about 20 wt% to about 80 wt% of dicalcium phosphate dihydrate, and from about about 0.5 wt% to about 12 wt% of HPC; - from about 0.5 wt% to about 7 wt% of a disintegrant, e.g., sodium starch glycolate; and - from about 0.1 wt% to about 5 wt% of a lubricant, e.g., glycerol dibehenate. [0356] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 10 wt% to about 70 wt% amorphous vamorolone, from about 10 wt% to about 70 wt% of lactose, from about 2 wt% to about 30 wt% starch, and from about about 0.5 wt% to about 12 wt% of povidone (e.g., K30); - from about 0.5 wt% to about 7 wt% of a disintegrant, e.g., sodium starch glycolate; and - from about 0.1 wt% to about 5 wt% of a lubricant, e.g., magnesium stearate. [0357] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 20 wt% to about 50 wt% amorphous vamorolone, from about 10 wt% to about 70 wt% of povidone (e.g., PVP K30), and from about 2.5 wt% to about 7.5 wt% poly(ethylene glycol) (e.g., PEG-4000); - from about 55 wt% to about 80 wt% of a diluent, e.g., silicified microcrystalline cellulose (e.g., PROSOLV® HD90); - from about 2 wt% to about 8 wt% of a disintegrant, e.g., sodium starch glycolate; and - from about 0.1 wt% to about 3 wt% of a lubricant, e.g., magnesium stearate. [0358] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising from about 40 wt% to about 60 wt% amorphous vamorolone and from about 40 wt% to about 60 wt% of a polymer, e.g., cellulose acetate phthalate (CAP); - from about 40 wt% to about 60 wt% of a diluent, e.g., silicified microcrystalline cellulose (e.g., PROSOLV® HD90); - from about 2 wt% to about 8 wt% of a disintegrant, e.g., sodium starch glycolate; and
- from about 0.1 wt% to about 3 wt% of a lubricant, e.g., magnesium stearate. [0359] In some aspects, the pharmaceutical composition can comprise: - an amorphous solid dispersion comprising about 20 wt% amorphous vamorolone and about 80 wt% of a polymer, e.g., hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose, methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), or polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®); - from about 10 wt% to about 20 wt% of a first diluent, e.g., microcrystalline cellulose (e.g., AVICEL® 105); - from about 20 wt% to about 45 wt% of a second diluent, e.g., mannitol (e.g., PARTECK® M100); - about 2 wt% of a disintegrant, e.g., croscarmellose sodium (e.g., AC-DI- SOL®); and - from about 0.5 wt% to about 3 wt% of a lubricant, e.g., sodium stearyl fumarate (e.g., PRUV®). Powders for Suspension [0360] In some aspects, the solid oral dosage forms described above can be a powder for suspension. The amorphous solid dispersions or coated particles described above can be blended with one or more pharmaceutical excipients, e.g., excipients appropriate for a powder for suspension solid oral dosage form. [0361] In some aspects, the one or more pharmaceutically acceptable excipients can comprise one or more suspending agents, one or more buffering agents, one or more wetting agents, one or more preservatives, one or more flavoring agents, one or more flow enhancers, one or more antifoaming agents, or a combination of any of the foregoing. [0362] In some aspects, the pharmaceutical composition can comprise one or more suspending agents. In some aspects, the one or more suspending agents can comprise hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing.
[0363] In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 80 wt% of the one or more suspending agents. In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 80 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 80 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 80 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 80 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 80 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 80 wt%, or from about 75 wt% to about 80 wt% of the one or more suspending agents. [0364] In some aspects, the pharmaceutical composition can comprise about 20 wt% of the one or more suspending agents. In some aspects, the pharmaceutical composition can comprise about 5 wt%, about 10 wt%, about 15 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, or about 80 wt% of the one or more suspending agents. [0365] In some aspects, the pharmaceutical composition can comprise one or more buffering agents. In some aspects, the one or more buffering agents can comprise a citrate buffer, a phosphate buffer, a carbonate buffer, or a combination of any of the foregoing. [0366] In some aspects, the pharmaceutical composition can comprise from about 0.1 wt% to about 5 wt% of the one or more buffering agents. In some aspects, the pharmaceutical composition can comprise from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5
wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more buffering agents. [0367] In some aspects, the pharmaceutical composition can comprise about 2.5 wt% of the one or more buffering agents. In some aspects, the pharmaceutical composition can comprise about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 1.5 wt%, about 2 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, or about 5 wt% of the one or more buffering agents. [0368] In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 80 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 80 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 80 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 80 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 80 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 80 wt%, or from about 75 wt% to about 80 wt% of the one or more suspending agents, wherein the one or more suspending agents can comprise hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt%
to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more buffering agents, wherein the one or more buffering agents can comprise a citrate buffer, a phosphate buffer, a carbonate buffer, or a combination of any of the foregoing. [0369] In some aspects, the pharmaceutical composition can comprise one or more wetting agents. In some aspects, the one or more wetting agents can comprise sodium lauryl sulfate, a poloxamer, a polysorbate, or a combination of any of the foregoing. [0370] In some aspects, the pharmaceutical composition can comprise from about 0.1 wt% to about 10 wt% of the one or more wetting agents. In some aspects, the pharmaceutical composition can comprise from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more wetting agents. [0371] In some aspects, the pharmaceutical composition can comprise about 5 wt% of the one or more wetting agents. In some aspects, the pharmaceutical composition can comprise about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt% of the one or more wetting agents. [0372] In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from
about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 80 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 80 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 80 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 80 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 80 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 80 wt%, or from about 75 wt% to about 80 wt% of the one or more suspending agents, wherein the one or more suspending agents can comprise hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more buffering agents, wherein the one or more buffering agents can comprise a citrate buffer, a phosphate buffer, a carbonate buffer, or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to
about 10 wt% of the one or more wetting agents, wherein the one or more wetting agents can comprise sodium lauryl sulfate, a poloxamer, a polysorbate, or a combination of any of the foregoing. [0373] In some aspects, the pharmaceutical composition can comprise one or more preservatives. In some aspects, the one or more preservatives can comprise methyl paraben, propyl paraben, sodium benzoate, citric acid, ascorbic acid, or a combination of any of the foregoing. [0374] In some aspects, the pharmaceutical composition can comprise from about 0.1 wt% to about 5 wt% of the one or more preservatives. In some aspects, wherein the pharmaceutical composition can comprise from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more preservatives. [0375] In some aspects, the pharmaceutical composition can comprise about 3 wt% of the one or more preservatives. In some aspects, the pharmaceutical composition can comprise about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, or about 5 wt% of the one or more preservatives. [0376] In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 80 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt%
to about 80 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 80 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 80 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 80 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 80 wt%, or from about 75 wt% to about 80 wt% of the one or more suspending agents, wherein the one or more suspending agents can comprise hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more buffering agents, wherein the one or more buffering agents can comprise a citrate buffer, a phosphate buffer, a carbonate buffer, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more wetting agents, wherein the one or more wetting agents can comprise sodium lauryl sulfate, a poloxamer, a polysorbate, or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from
about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more preservatives, wherein the one or more preservatives can comprise methyl paraben, propyl paraben, sodium benzoate, citric acid, ascorbic acid, or a combination of any of the foregoing. [0377] In some aspects, the pharmaceutical composition can comprise one or more flavoring agents. In some aspects, the one or more flavoring agents can comprise sucrose, aspartame, an artificial flavor (e.g, peppermint, bubblegum, or grape), a natural flavor, or a combination of any of the foregoing. [0378] In some aspects, the pharmaceutical composition can comprise from about 0.1 wt% to about 5 wt% of the one or more flavoring agents. In some aspects, wherein the pharmaceutical composition can comprise from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more flavoring agents. [0379] In some aspects, the pharmaceutical composition can comprise about 3 wt% of the one or more flavoring agents. In some aspects, the pharmaceutical composition can comprise about 0.1 wt%, about 0.5 wt%, about 1 wt%, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, or about 5 wt% of the one or more flavoring agents. [0380] In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5
wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 80 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 80 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 80 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 80 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 80 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 80 wt%, or from about 75 wt% to about 80 wt% of the one or more suspending agents, wherein the one or more suspending agents can comprise hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more buffering agents, wherein the one or more buffering agents can comprise a citrate buffer, a phosphate buffer, a carbonate buffer, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from
about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more wetting agents, wherein the one or more wetting agents can comprise sodium lauryl sulfate, a poloxamer, a polysorbate, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more preservatives, wherein the one or more preservatives can comprise methyl paraben, propyl paraben, sodium benzoate, citric acid, ascorbic acid, or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more flavoring agents, wherein the one or more flavoring agents can comprise sucrose, aspartame, an artificial flavor (e.g, peppermint, bubblegum, or grape), a natural flavor, or a combination of any of the foregoing. [0381] In some aspects, the pharmaceutical composition can comprise one or more antifoaming agents. In some aspects, the one or more antifoaming agents can comprise simethicone (polydimethylsiloxane-silicon dioxide), an alcohol, e.g., cetostearyl alcohol, an insoluble oil, e.g., castor oil, a stearate, a polydimethylsiloxane or other silicone derivative, an ether, a glycol, or a combination of any of the foregoing. [0382] In some aspects, the pharmaceutical composition can comprise from about 0.01 wt% to about 10 wt% of the one or more antifoaming agents. In some aspects, the
pharmaceutical composition can comprise from about 0.01 wt% to about 0.1 wt%, from about 0.01 wt% to about 0.5 wt%, from about 0.01 wt% to about 1 wt%, from about 0.01 wt% to about 2.5 wt%, from about 0.01 wt% to about 5 wt%, from about 0.01 wt% to about 7.5 wt%, from about 0.01 wt% to about 10 wt%, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more antifoaming agents. [0383] In some aspects, the pharmaceutical composition can comprise about 1 wt% of the one or more antifoaming agents. In some aspects, the pharmaceutical composition can comprise about 1 wt% of the one or more antifoaming agents. [0384] In some aspects, the pharmaceutical composition can comprise from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 80 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 80 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 80 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 80 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 80 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 80 wt%, or from about 75 wt% to about 80 wt% of the one or more suspending
agents, wherein the one or more suspending agents can comprise hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, carbomer, xantham gum, starch, pregelatinized starch, sodium alginate, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more buffering agents, wherein the one or more buffering agents can comprise a citrate buffer, a phosphate buffer, a carbonate buffer, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more wetting agents, wherein the one or more wetting agents can comprise sodium lauryl sulfate, a poloxamer, a polysorbate, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more preservatives, wherein the one or
more preservatives can comprise methyl paraben, propyl paraben, sodium benzoate, citric acid, ascorbic acid, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.1 wt% to about 4 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 1 wt% to about 5 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, from about 2 wt% to about 5 wt%, from about 3 wt% to about 4 wt%, from about 3 wt% to about 5 wt%, or from about 4 wt% to about 5 wt% of the one or more flavoring agents, wherein the one or more flavoring agents can comprise sucrose, aspartame, an artificial flavor (e.g, peppermint, bubblegum, or grape), a natural flavor, or a combination of any of the foregoing, and from about 0.01 wt% to about 0.1 wt%, from about 0.01 wt% to about 0.5 wt%, from about 0.01 wt% to about 1 wt%, from about 0.01 wt% to about 2.5 wt%, from about 0.01 wt% to about 5 wt%, from about 0.01 wt% to about 7.5 wt%, from about 0.01 wt% to about 10 wt%, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2.5 wt%, from about 0.1 wt% to about 5 wt%, from about 0.1 wt% to about 7.5 wt%, from about 0.1 wt% to about 10 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 0.5 wt% to about 10 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more antifoaming agents, wherein the one or more antifoaming agents can comprise simethicone (polydimethylsiloxane-silicon dioxide), an alcohol, e.g., cetostearyl alcohol, an insoluble oil, e.g., castor oil, a stearate, a polydimethylsiloxane or other silicone derivative, an ether, a glycol, or a combination of any of the foregoing. [0385] In some aspects, the pharmaceutical composition can comprise: - from about 1 wt % to about 90 wt % of vamorolone relative to the total mass of the pharmaceutical composition;
- from about 20 wt% to about 90 wt% of any of the amorphous solid dispersions described above; - from about 5 wt% to about 80 wt% of one or more suspending agents, e.g., HPC, HPMC, sodium carboxymethylcellulose, carbomer, xanthan gum, starch, pregelatinized starch, or sodium alginate; - optionally from about 0.1 wt% to about 5 wt% of one or more buffering agents, e.g., citrate/citric acid; - optionally from about 0.1 wt% to about 5 wt% of one or more wetting agenets, e.g., sodium lauryl sulfate, poloxamer 188, and/or polysorbate 80; - optionally from about 0.1 wt% to about 5 wt% of one or more preservatives, eg., methyl paraben, propyl paraben, and/or sodium benzoate; - optionally from about 0.1 wt% to about 5 wt% of one or more flavoring agents, e.g., sucrose, aspartame, an artificial flavor (e.g., peppermint, bubblegum, or grape), and/or a natural flavor; - optionally from about 0.1 wt% to about 5 wt% of one or more flow enhancers, e.g., colloidal silicon dioxide and/or talc; and - optionally from about 0.01 wt% to about 10 wt% of one or more antifoaming agents, e.g., simethicone. [0386] In some aspects, the pharmaceutical composition can comprise: - from about 2 wt% to about 54 wt% of vamorolone relative to the total mass of the pharmaceutical composition; - from about 20 wt% to about 90 wt% of an amorphous solid dispersion comprising from about 10 wt% to about 60 wt% amorphous vamorolone, from about 10 wt% to about 80 wt% of a polymer, optionally a plasticizer, optionally a surfactant, and optionally a filler; - from about 5 wt% to about 80 wt% of one or more suspending agents, e.g., HPC, HPMC, sodium carboxymethylcellulose, carbomer, xanthan gum, starch, pregelatinized starch, or sodium alginate; - optionally from about 0.1 wt% to about 5 wt% of one or more buffering agents, e.g., citrate/citric acid; - optionally from about 0.1 wt% to about 5 wt% of one or more wetting agents, e.g., sodium lauryl suflate, poloxamer 188, and/or polysorbate 80;
- optionally from about 0.1 wt% to about 5 wt% of one or more flavoring agents, e.g., sucrose, aspartame, an artificial flavor (e.g., peppermint, bubblegum, or grape), and/or a natural flavor; - optionally from about 0.1 wt% to about 5 wt% of one or more flow enhancers, e.g., colloidal silicon dioxide and/or talc; and - optionally from about 0.01 wt% to about 10 wt% of one or more antifoaming agents, e.g., simethicone. Pharmaceutical Compositions Comprising Crystalline Vamorolone [0387] In certain embodiments, the present disclosure also provides a pharmaceutical composition comprising crystalline vamorolone and one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is a solid oral dosage form. [0388] In certain embodiments, the present disclosure also provides a pharmaceutical composition comprising crystalline vamorolone, one or more pharmaceutically acceptable excipients, and an amorphous solid dispersion described above, wherein the pharmaceutical composition is a solid oral dosage form. [0389] In some aspects, the crystalline vamorolone is vamorolone crystalline Form I, Form II, Form III, Form IV, Form V, Form VI, Form VII, Form VIII, or any combination of the foregoing. In some aspects, the crystalline vamorolone is vamorolone crystalline Form I. [0390] In some aspects, the pharmaceutical composition can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from
about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, from about 85 wt% to about 95 wt%, from about 90 wt% to about 95 wt%, from about 90 wt% to about 96 wt%, from about 90 wt% to about 97 wt%, from about 90 wt% to about 98 wt%, from about 92 wt% to about 95 wt%, from about 92 wt% to about 97 wt%, or from about 93 wt% to about 98 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I. [0391] In some aspects, the one or more pharmaceutically acceptable excipients can comprise one or more diluents, one or more binders, one or more disintegrants, one or more lubricants, or a combination of any of the foregoing. [0392] In some aspects, the pharmaceutical composition can comprise one or more diluents. In some aspects, the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, lactose, starch, dicalcium phosphate dihydrate, or a combination of any of the foregoing. [0393] In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 85 wt% of the one or more diluents. In some aspects, the pharmaceutical composition can comprise from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 85 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 85 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 85 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, or from about 80 wt% to about 85 wt% of the one or more diluents. [0394] In some aspects, the pharmaceutical composition can comprise about 20 wt% of the one or more diluents. In some aspects, the pharmaceutical composition can comprise about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%,
about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, or about 85 wt% of the one or more diluents. [0395] In some aspects, the pharmaceutical composition can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% crystalline vamorolone and from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 85 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 85 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 85 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, or from about 80 wt% to about 85 wt% of the one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified
microcrystalline cellulose, mannitol, lactose, starch, dicalcium phosphate dihydrate, or a combination of any of the foregoing. [0396] In some aspects, the pharmaceutical composition can comprise one or more binders. In some aspects, the one or more binders can comprise povidone, copovidone, hydroxpropylmethyl cellulose, hydroxypropyl cellulose, or a combination of any of the foregoing. [0397] In some aspects, the pharmaceutical composition can comprise from about 0.5 wt% to about 10 wt% of the one or more binders. In some aspects, the pharmaceutical composition can comprise from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more binders. [0398] In some aspects, the pharmaceutical composition can comprise about 0.5 wt% of the one or more binders. In some aspects, the pharmaceutical composition can comprise about 1 wt%, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, about 5 wt%, about 5.5 wt%, about 6 wt%, about 6.5 wt%, about 7 wt%, about 7.5 wt%, about 8 wt%, about 8.5 wt%, about 9 wt%, about 9.5 wt%, or about 10 wt% of the one or more binders. [0399] In some aspects, the pharmaceutical composition can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from
about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 85 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 85 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 85 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, or from about 80 wt% to about 85 wt% of the one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, lactose, starch, dicalcium phosphate dihydrate, or a combination of any of the foregoing, and from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more binders, wherein the one or more binders can comprise povidone, copovidone, hydroxpropylmethyl cellulose, hydroxypropyl cellulose, or a combination of any of the foregoing. [0400] In some aspects, the pharmaceutical composition can comprise one or more disintegrants. In some aspects, the one or more disintegrants can comprise crosscarmellose sodium, sodium starch glycolate (EXPLOTAB®), cross povidone, or a combination of any of the foregoing.
[0401] In some aspects, the pharmaceutical composition can comprise from about 0.5 wt% to about 7 wt% of the one or more disintegrants. In some aspects, the pharmaceutical composition can comprise from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, or from about 5 wt% to about 7 wt% of the one or more disintegrants. [0402] In some aspects, the pharmaceutical composition can comprise about 0.5 wt% of the one or more disintegrants. In some aspects, the pharmaceutical composition can comprise about 1 wt%, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, about 5 wt%, about 5.5 wt%, about 6 wt%, about 6.5 wt%, or about 7 wt% of the one or more disintegrants. [0403] In some aspects, the pharmaceutical composition can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt%
to about 80 wt%, from about 30 wt% to about 85 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 85 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 85 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, or from about 80 wt% to about 85 wt% of the one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, lactose, starch, dicalcium phosphate dihydrate, or a combination of any of the foregoing, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more binders, wherein the one or more binders can comprise povidone, copovidone, hydroxpropylmethyl cellulose, hydroxypropyl cellulose, or a combination of any of the foregoing, and from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, or from about 5 wt% to about 7 wt% of the one or more disintegrants, wherein the one or more disintegrants can comprise crosscarmellose sodium, sodium starch glycolate (EXPLOTAB®), cross povidone, or a combination of any of the foregoing. [0404] In some aspects, the pharmaceutical composition can comprise one or more lubricants. In some aspects, one or more lubricants can comprise magnesium stearate, steric acid, glyceryl dibehenate, sodium steryl fumarate, or a combination of any of the foregoing. [0405] In some aspects, the pharmaceutical composition can comprise from about 0.1 wt% to about 4 wt% of the one or more lubricants. In some aspects, the pharmaceutical composition can comprise from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to
about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, or from about 3 wt% to about 4 wt% of the one or more lubricants. [0406] In some aspects, the pharmaceutical composition can comprise about 0.1 wt% of the one or more lubricants. In some aspects, the pharmaceutical composition can comprise about 0.5 wt%, about 1 wt%, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, or about 4 wt% of the one or more lubricants. [0407] In some aspects, the pharmaceutical composition can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 85 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from
about 40 wt% to about 80 wt%, from about 40 wt% to about 85 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 85 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, or from about 80 wt% to about 85 wt% of the one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, lactose, starch, dicalcium phosphate dihydrate, or a combination of any of the foregoing, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more binders, wherein the one or more binders can comprise povidone, copovidone, hydroxpropylmethyl cellulose, hydroxypropyl cellulose, or a combination of any of the foregoing, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, or from about 5 wt% to about 7 wt% of the one or more disintegrants, wherein the one or more disintegrants can comprise crosscarmellose sodium, sodium starch glycolate (EXPLOTAB®), cross povidone, or a combination of any of the foregoing, and from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, or from about 3 wt% to about 4 wt% of the one or more lubricants, wherein one or more lubricants can comprise magnesium stearate, steric acid, glyceryl dibehenate, sodium steryl fumarate, or a combination of any of the foregoing.
[0408] In some aspects, the pharmaceutical composition can comprise from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7 wt%, from about 0.5 wt% to about 10 wt%, from about 0.5 wt% to about 20 wt%, from about 0.5 wt% to about 30 wt%, from about 0.5 wt% to about 40 wt%, from about 0.5 wt% to about 50 wt%, from about 0.5 wt% to about 70 wt%, from about 0.5 wt% to about 90 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, from about 3 wt% to about 10 wt%, from about 3 wt% to about 20 wt%, from about 3 wt% to about 30 wt%, from about 3 wt% to about 40 wt%, from about 3 wt% to about 50 wt%, from about 3 wt% to about 70 wt%, from about 3 wt% to about 90 wt%, from about 5 wt% to about 7 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 40 wt%, from about 5 wt% to about 50 wt%, from about 5 wt% to about 70 wt%, from about 5 wt% to about 90 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%, from about 10 wt% to about 50 wt%, from about 10 wt% to about 70 wt%, from about 10 wt% to about 90 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 70 wt%, or from about 70 wt% to about 90 wt% of an amorphous solid dispersion described above. [0409] In some aspects, the pharmaceutical composition can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from
about 75 wt% to about 95 wt%, from about 85 wt% to about 95 wt%, from about 90 wt% to about 95 wt%, from about 90 wt% to about 96 wt%, from about 90 wt% to about 97 wt%, from about 90 wt% to about 98 wt%, from about 92 wt% to about 95 wt%, from about 92 wt% to about 97 wt%, or from about 93 wt% to about 98 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, and from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7 wt%, from about 0.5 wt% to about 10 wt%, from about 0.5 wt% to about 20 wt%, from about 0.5 wt% to about 30 wt%, from about 0.5 wt% to about 40 wt%, from about 0.5 wt% to about 50 wt%, from about 0.5 wt% to about 70 wt%, from about 0.5 wt% to about 90 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, from about 3 wt% to about 10 wt%, from about 3 wt% to about 20 wt%, from about 3 wt% to about 30 wt%, from about 3 wt% to about 40 wt%, from about 3 wt% to about 50 wt%, from about 3 wt% to about 70 wt%, from about 3 wt% to about 90 wt%, from about 5 wt% to about 7 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 40 wt%, from about 5 wt% to about 50 wt%, from about 5 wt% to about 70 wt%, from about 5 wt% to about 90 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%, from about 10 wt% to about 50 wt%, from about 10 wt% to about 70 wt%, from about 10 wt% to about 90 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 70 wt%, or from about 70 wt% to about 90 wt% of an amorphous solid dispersion described above. [0410] In some aspects, the pharmaceutical composition can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85
wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, from about 85 wt% to about 95 wt%, from about 90 wt% to about 95 wt%, from about 90 wt% to about 96 wt%, from about 90 wt% to about 97 wt%, from about 90 wt% to about 98 wt%, from about 92 wt% to about 95 wt%, from about 92 wt% to about 97 wt%, or from about 93 wt% to about 98 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 85 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 85 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 85 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, or from about 80 wt% to about 85 wt% of the one or more diluents, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more binders, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, or from about 5 wt% to about 7 wt% of the one or more disintegrants, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from
about 0.1 wt% to about 3 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, or from about 3 wt% to about 4 wt% of the one or more lubricants, and from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7 wt%, from about 0.5 wt% to about 10 wt%, from about 0.5 wt% to about 20 wt%, from about 0.5 wt% to about 30 wt%, from about 0.5 wt% to about 40 wt%, from about 0.5 wt% to about 50 wt%, from about 0.5 wt% to about 70 wt%, from about 0.5 wt% to about 90 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, from about 3 wt% to about 10 wt%, from about 3 wt% to about 20 wt%, from about 3 wt% to about 30 wt%, from about 3 wt% to about 40 wt%, from about 3 wt% to about 50 wt%, from about 3 wt% to about 70 wt%, from about 3 wt% to about 90 wt%, from about 5 wt% to about 7 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 40 wt%, from about 5 wt% to about 50 wt%, from about 5 wt% to about 70 wt%, from about 5 wt% to about 90 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%, from about 10 wt% to about 50 wt%, from about 10 wt% to about 70 wt%, from about 10 wt% to about 90 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 70 wt%, or from about 70 wt% to about 90 wt% of an amorphous solid dispersion described above. [0411] In some aspects, the pharmaceutical composition can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85
wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, from about 85 wt% to about 95 wt%, from about 90 wt% to about 95 wt%, from about 90 wt% to about 96 wt%, from about 90 wt% to about 97 wt%, from about 90 wt% to about 98 wt%, from about 92 wt% to about 95 wt%, from about 92 wt% to about 97 wt%, or from about 93 wt% to about 98 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 85 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 85 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 85 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, or from about 80 wt% to about 85 wt% of the one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, lactose, starch, dicalcium phosphate dihydrate, or a combination of any of the foregoing, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more binders, wherein the one or more binders can comprise povidone, copovidone, hydroxpropylmethyl cellulose, hydroxypropyl cellulose, or a combination of any of the foregoing, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from
about 0.5 wt% to about 5 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, or from about 5 wt% to about 7 wt% of the one or more disintegrants, wherein the one or more disintegrants can comprise crosscarmellose sodium, sodium starch glycolate (EXPLOTAB®), cross povidone, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, or from about 3 wt% to about 4 wt% of the one or more lubricants, wherein one or more lubricants can comprise magnesium stearate, steric acid, glyceryl dibehenate, sodium steryl fumarate, or a combination of any of the foregoing, and from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7 wt%, from about 0.5 wt% to about 10 wt%, from about 0.5 wt% to about 20 wt%, from about 0.5 wt% to about 30 wt%, from about 0.5 wt% to about 40 wt%, from about 0.5 wt% to about 50 wt%, from about 0.5 wt% to about 70 wt%, from about 0.5 wt% to about 90 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, from about 3 wt% to about 10 wt%, from about 3 wt% to about 20 wt%, from about 3 wt% to about 30 wt%, from about 3 wt% to about 40 wt%, from about 3 wt% to about 50 wt%, from about 3 wt% to about 70 wt%, from about 3 wt% to about 90 wt%, from about 5 wt% to about 7 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 40 wt%, from about 5 wt% to about 50 wt%, from about 5 wt% to about 70 wt%, from about 5 wt% to about 90 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%, from about 10 wt% to about 50 wt%, from about 10 wt% to about 70 wt%, from about 10 wt% to about 90 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 70 wt%, or from about 70 wt% to about 90 wt% of an amorphous solid dispersion comprising vamorolone described above. [0412] In some aspects, the pharmaceutical composition can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about
45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, from about 85 wt% to about 95 wt%, from about 90 wt% to about 95 wt%, from about 90 wt% to about 96 wt%, from about 90 wt% to about 97 wt%, from about 90 wt% to about 98 wt%, from about 92 wt% to about 95 wt%, from about 92 wt% to about 97 wt%, or from about 93 wt% to about 98 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, and from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7 wt%, from about 0.5 wt% to about 10 wt%, from about 0.5 wt% to about 20 wt%, from about 0.5 wt% to about 30 wt%, from about 0.5 wt% to about 40 wt%, from about 0.5 wt% to about 50 wt%, from about 0.5 wt% to about 70 wt%, from about 0.5 wt% to about 90 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, from about 3 wt% to about 10 wt%, from about 3 wt% to about 20 wt%, from about 3 wt% to about 30 wt%, from about 3 wt% to about 40 wt%, from about 3 wt% to about 50 wt%, from about 3 wt% to about 70 wt%, from about 3 wt% to about 90 wt%, from about 5 wt% to about 7 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 40 wt%, from about 5 wt% to about 50 wt%, from about 5 wt% to about 70 wt%, from about 5 wt% to about 90 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%, from about 10 wt% to about 50 wt%, from about 10 wt% to about 70 wt%, from about 10 wt% to about 90 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt%
to about 70 wt%, or from about 70 wt% to about 90 wt% of an amorphous solid dispersion, wherein the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone and from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of a polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS,
which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. [0413] In some aspects, the pharmaceutical composition can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, from about 85 wt% to about 95 wt%, from about 90 wt% to about 95 wt%, from about 90 wt% to about 96 wt%, from about 90 wt% to about 97 wt%, from about 90 wt% to about 98 wt%, from about 92 wt% to about 95 wt%, from about 92 wt% to about 97 wt%, or from about 93 wt% to about 98 wt% crystalline
vamorolone, e.g., crystalline vamorolone Form I, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 85 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 85 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 85 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, or from about 80 wt% to about 85 wt% of the one or more diluents, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more binders, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, or from about 5 wt% to about 7 wt% of the one or more disintegrants, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, or from about 3 wt% to about 4 wt% of the one or more lubricants, and from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7 wt%, from about 0.5 wt% to about 10 wt%, from about 0.5 wt% to about 20 wt%, from about 0.5 wt% to about 30 wt%, from about 0.5 wt% to about
40 wt%, from about 0.5 wt% to about 50 wt%, from about 0.5 wt% to about 70 wt%, from about 0.5 wt% to about 90 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, from about 3 wt% to about 10 wt%, from about 3 wt% to about 20 wt%, from about 3 wt% to about 30 wt%, from about 3 wt% to about 40 wt%, from about 3 wt% to about 50 wt%, from about 3 wt% to about 70 wt%, from about 3 wt% to about 90 wt%, from about 5 wt% to about 7 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 40 wt%, from about 5 wt% to about 50 wt%, from about 5 wt% to about 70 wt%, from about 5 wt% to about 90 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%, from about 10 wt% to about 50 wt%, from about 10 wt% to about 70 wt%, from about 10 wt% to about 90 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 70 wt%, or from about 70 wt% to about 90 wt% of an amorphous solid, wherein the amorphous solid dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone and from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from
about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of a polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. [0414] In some aspects, the pharmaceutical composition can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65
wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, from about 85 wt% to about 95 wt%, from about 90 wt% to about 95 wt%, from about 90 wt% to about 96 wt%, from about 90 wt% to about 97 wt%, from about 90 wt% to about 98 wt%, from about 92 wt% to about 95 wt%, from about 92 wt% to about 97 wt%, or from about 93 wt% to about 98 wt% crystalline vamorolone, e.g., crystalline vamorolone Form I, from about 20 wt% to about 30 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 60 wt%, from about 20 wt% to about 70 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 40 wt%, from about 30 wt% to about 50 wt%, from about 30 wt% to about 60 wt%, from about 30 wt% to about 70 wt%, from about 30 wt% to about 80 wt%, from about 30 wt% to about 85 wt%, from about 40 wt% to about 50 wt%, from about 40 wt% to about 60 wt%, from about 40 wt% to about 70 wt%, from about 40 wt% to about 80 wt%, from about 40 wt% to about 85 wt%, from about 50 wt% to about 60 wt%, from about 50 wt% to about 70 wt%, from about 50 wt% to about 80 wt%, from about 50 wt% to about 85 wt%, from about 60 wt% to about 70 wt%, from about 60 wt% to about 80 wt%, from about 60 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, from about 70 wt% to about 80 wt%, from about 70 wt% to about 85 wt%, or from about 80 wt% to about 85 wt% of the one or more diluents, wherein the one or more diluents can comprise microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, lactose, starch, dicalcium phosphate dihydrate, or a combination of any of the foregoing, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2.5 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7.5 wt%, from about 1 wt% to about 2.5 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7.5 wt%, from about 1 wt% to about 10 wt%, from about 2.5 wt% to about 5 wt%, from about 2.5 wt% to about 7.5 wt%, from about 2.5 wt% to about 10 wt%, from about 5 wt% to about 7.5 wt%, from about 5 wt% to about 10 wt%, or from about 7.5 wt% to about 10 wt% of the one or more binders,
wherein the one or more binders can comprise povidone, copovidone, hydroxpropylmethyl cellulose, hydroxypropyl cellulose, or a combination of any of the foregoing, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 5 wt%, from about 1 wt% to about 7 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, or from about 5 wt% to about 7 wt% of the one or more disintegrants, wherein the one or more disintegrants can comprise crosscarmellose sodium, sodium starch glycolate (EXPLOTAB®), cross povidone, or a combination of any of the foregoing, from about 0.1 wt% to about 0.5 wt%, from about 0.1 wt% to about 1 wt%, from about 0.1 wt% to about 2 wt%, from about 0.1 wt% to about 3 wt%, from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 2 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 4 wt%, from about 1 wt% to about 2 wt%, from about 1 wt% to about 3 wt%, from about 1 wt% to about 4 wt%, from about 2 wt% to about 3 wt%, from about 2 wt% to about 4 wt%, or from about 3 wt% to about 4 wt% of the one or more lubricants, wherein one or more lubricants can comprise magnesium stearate, steric acid, glyceryl dibehenate, sodium steryl fumarate, or a combination of any of the foregoing, and from about 0.5 wt% to about 1 wt%, from about 0.5 wt% to about 3 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 7 wt%, from about 0.5 wt% to about 10 wt%, from about 0.5 wt% to about 20 wt%, from about 0.5 wt% to about 30 wt%, from about 0.5 wt% to about 40 wt%, from about 0.5 wt% to about 50 wt%, from about 0.5 wt% to about 70 wt%, from about 0.5 wt% to about 90 wt%, from about 3 wt% to about 5 wt%, from about 3 wt% to about 7 wt%, from about 3 wt% to about 10 wt%, from about 3 wt% to about 20 wt%, from about 3 wt% to about 30 wt%, from about 3 wt% to about 40 wt%, from about 3 wt% to about 50 wt%, from about 3 wt% to about 70 wt%, from about 3 wt% to about 90 wt%, from about 5 wt% to about 7 wt%, from about 5 wt% to about 10 wt%, from about 5 wt% to about 20 wt%, from about 5 wt% to about 30 wt%, from about 5 wt% to about 40 wt%, from about 5 wt% to about 50 wt%, from about 5 wt% to about 70 wt%, from about 5 wt% to about 90 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 30 wt%, from about 10 wt% to about 40 wt%, from about 10 wt% to about 50 wt%, from about 10 wt% to about 70 wt%, from about 10 wt% to about 90 wt%, from about 20 wt% to about 40 wt%, from about 20 wt% to about 50 wt%, from about 20 wt% to about 70 wt%, or from about 70 wt% to about 90 wt% of an amorphous solid dispersion, wherein the amorphous solid
dispersion can comprise from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 25 wt% to about 95 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 35 wt% to about 95 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 45 wt% to about 95 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 55 wt% to about 95 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, from about 65 wt% to about 95 wt%, from about 75 wt% to about 85 wt%, from about 75 wt% to about 95 wt%, or from about 85 wt% to about 95 wt% amorphous vamorolone and from about 5 wt% to about 15 wt%, from about 5 wt% to about 25 wt%, from about 5 wt% to about 35 wt%, from about 5 wt% to about 45 wt%, from about 5 wt% to about 55 wt%, from about 5 wt% to about 65 wt%, from about 5 wt% to about 75 wt%, from about 15 wt% to about 25 wt%, from about 15 wt% to about 35 wt%, from about 15 wt% to about 45 wt%, from about 15 wt% to about 55 wt%, from about 15 wt% to about 65 wt%, from about 15 wt% to about 75 wt%, from about 15 wt% to about 85 wt%, from about 25 wt% to about 35 wt%, from about 25 wt% to about 45 wt%, from about 25 wt% to about 55 wt%, from about 25 wt% to about 65 wt%, from about 25 wt% to about 75 wt%, from about 25 wt% to about 85 wt%, from about 35 wt% to about 45 wt%, from about 35 wt% to about 55 wt%, from about 35 wt% to about 65 wt%, from about 35 wt% to about 75 wt%, from about 35 wt% to about 85 wt%, from about 45 wt% to about 55 wt%, from about 45 wt% to about 65 wt%, from about 45 wt% to about 75 wt%, from about 45 wt% to about 85 wt%, from about 55 wt% to about 65 wt%, from about 55 wt% to about 75 wt%, from about 55 wt% to about 85 wt%, from about 65 wt% to about 75 wt%, from about 65 wt% to about 85 wt%, or from about 75 wt% to about 85 wt% of a polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as
hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA- 64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. [0415] In some aspects, the pharmaceutical composition is prepared by direct blending. [0416] In some aspects, the pharmaceutical composition can comprise: - from about 10 wt% to about 70 wt% crystalline vamorolone; - from about 10 wt% to about 65 wt% of a first diluent, e.g., microcrystalline cellulose, silicified microcrystalline cellulose, or mannitol; - from about 5 wt% to about 30 wt% of a second diluent, e.g., lactose, starch, or dicalcium phosphate dihydrate; - from about 0.5 wt% to about 15 wt% of a binder, e.g., povidone, copovidone, HPMC, or HPC; - from about 0.5 wt% to about 10 wt% of a disintegrant, e.g., crosscarmellose sodium, sodium starch glycolate, or cross povidone; and - from about 0.1 wt% to about 5 wt% of a lubricant, e.g., magnesium stearate, steric acid, glyceryl dibehenate, or sodium steryl fumarate. [0417] In some aspects, the pharmaceutical composition can comprise: - from about 10 wt% to about 70 wt% crystalline vamorolone; - from about 10 wt% to about 65 wt% of a first diluent, e.g., microcrystalline cellulose, silicified microcrystalline cellulose, or mannitol; - optionally from about 5 wt% to about 30 wt% of a second diluent, e.g., lactose, starch, or dicalcium phosphate dihydrate; - from about 0.5 wt% to about 15 wt% of a binder, e.g., povidone, copovidone, HPMC, or HPC;
- from about 0.5 wt% to about 10 wt% of a disintegrant, e.g., crosscarmellose sodium, sodium starch glycolate, or cross povidone; - from about 0.1 wt% to about 5 wt% of a lubricant, e.g., magnesium stearate, steric acid, glyceryl dibehenate, or sodium steryl fumarate; and - from about 0.5 wt% to about 5 wt% of an amorphous solid dispersion comprising vamorolone described above. [0418] In some aspects, the pharmaceutical composition can comprise: - from about 10 wt% to about 90 wt% crystalline vamorolone; - from about 10 wt% to about 65 wt% of a first diluent, e.g., microcrystalline cellulose, silicified microcrystalline cellulose, or mannitol; - optionally from about 5 wt% to about 30 wt% of a second diluent, e.g., lactose, starch, or dicalcium phosphate dihydrate; - from about 0.5 wt% to about 15 wt% of a binder, e.g., povidone, copovidone, HPMC, or HPC; - from about 0.5 wt% to about 10 wt% of a disintegrant, e.g., crosscarmellose sodium, sodium starch glycolate, or cross povidone; - from about 0.1 wt% to about 5 wt% of a lubricant, e.g., magnesium stearate, steric acid, glyceryl dibehenate, or sodium steryl fumarate; and - from about 0.5 wt% to about 5 wt% of an amorphous solid dispersion, wherein the amorphous solid dispersion can comprise from about 5 wt% to about 50 wt% vamorolone and from about 50 wt% to about 95 wt % of a polymer. [0419] In some aspects, the pharmaceutical composition can comprise: - from about 10 wt% to about 90 wt% crystalline vamorolone; - from about 10 wt% to about 65 wt% of a first diluent, e.g., microcrystalline cellulose, silicified microcrystalline cellulose, or mannitol; - optionally from about 5 wt% to about 30 wt% of a second diluent, e.g., lactose, starch, or dicalcium phosphate dihydrate; - from about 0.5 wt% to about 15 wt% of a binder, e.g., povidone, copovidone, HPMC, or HPC; - from about 0.5 wt% to about 10 wt% of a disintegrant, e.g., crosscarmellose sodium, sodium starch glycolate, or cross povidone; - from about 0.1 wt% to about 5 wt% of a lubricant, e.g., magnesium stearate, steric acid, glyceryl dibehenate, or sodium steryl fumarate; and
- from about 0.5 wt% to about 5 wt% of an amorphous solid dispersion, wherein the amorphous solid dispersion can comprise from about 5 wt% to about 50 wt% vamorolone and from about 50 wt% to about 95 wt % of a polymer, wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS, which can have any grade, e.g., L, M, or H), hydroxypropyl methylcellulose (HPMC, also referred to as hypromellose, which can have any grade, e.g., E3, E5, or E15), hydroxypropyl cellulose (HPC or KLUCEL™, which can have any molecular weight, e.g., 40,000), hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, povidone (which can have any grade, e.g., K-12, K-17, K-25, K-30), copovidone (e.g., KOLLIDON® VA-64), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOLUPLUS®), methacrylic acid-ethyl acrylate copolymer (1:1) (EUDRAGIT® L-55), methacrylic acid-methyl methacrylate copolymer (1:1) (EUDRAGIT® L), methacrylic acid-methyl methacrylate copolymer (1:2) (EUDRAGIT® S), amino methacrylate copolymer (EUDRAGIT® E), poly(ethylene glycol), poly(ethylene oxide) (which can have any molecular weight, e.g., from about 3,000 to about 20,000,000, and in particular aspects from about 3,000 to about 8,000), poly(vinyl acetate), polyvinyl alcohol, poly(acrylic acid) (e.g., APINOVEX™ LV), or any combination of the foregoing. Properties of Pharmaceutical Compositions [0420] In some aspects, a pharmaceutical composition described herein can have a total mass ranging from about 50 mg to about 1,000 mg. In some aspects, a pharmaceutical composition described herein can have a total mass ranging from about 50 mg to about 100 mg, from about 50 mg to about 200 mg, from about 50 mg to about 300 mg, from about 50 mg to about 400 mg, from about 50 mg to about 500 mg, from about 50 mg to about 600 mg, from about 50 mg to about 700 mg, from about 50 mg to about 800 mg, from about 50 mg to about 900 mg, from about 50 mg to about 1,000 mg, from about 100 mg to about 200 mg, from about 100 mg to about 300 mg, from about 100 mg to about 400 mg, from about 100 mg to about 500 mg, from about 100 mg to about 600 mg, from about 100 mg to about 700 mg, from about 100 mg to about 800 mg, from about 100 mg to about 900 mg, from about 200 mg to about 300 mg, from about 200 mg to about 400
mg, from about 200 mg to about 500 mg, from about 200 mg to about 600 mg, from about 200 mg to about 700 mg, from about 200 mg to about 800 mg, from about 200 mg to about 900 mg, from about 200 mg to about 1,000 mg, from about 300 mg to about 400 mg, from about 300 mg to about 500 mg, from about 300 mg to about 600 mg, from about 300 mg to about 700 mg, from about 300 mg to about 800 mg, from about 300 mg to about 900 mg, from about 300 mg to about 1,000 mg, from about 400 mg to about 500 mg, from about 400 mg to about 600 mg, from about 400 mg to about 700 mg, from about 400 mg to about 800 mg, from about 400 mg to about 900 mg, from about 400 mg to about 1,000 mg, from about 500 mg to about 600 mg, from about 500 mg to about 700 mg, from about 500 mg to about 800 mg, from about 500 mg to about 900 mg, from about 500 mg to about 1,000 mg, from about 600 mg to about 700 mg, from about 600 mg to about 800 mg, from about 600 mg to about 900 mg, from about 600 mg to about 1,000 mg, from about 700 mg to about 800 mg, from about 700 mg to about 900 mg, from about 700 mg to about 1,000 mg, from about 800 mg to about 900 mg, from about 800 mg to about 1,000 mg, or from about 900 mg to about 1,000 mg. [0421] In some aspects, a pharmaceutical composition described herein can have a total mass of about 300 mg. In some aspects, a pharmaceutical composition described herein can have a total mass of about 50 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, or about 1,000 mg. [0422] In some aspects, a pharmaceutical composition described herein can have a friability of less than 1.0% as measured using USP<1216>. In some aspects, a pharmaceutical composition described herein can have a friability of less than 5%, less than 2.5%, less than 0.9%, less than 0.8%, less than 0.7%, less than 0.6%, less than 0.5%, less than 0.4%, or less than 0.3% as measured using USP<1216>. [0423] In some aspects, a pharmaceutical composition described herein can have a disintegration time of less than 10 minutes. In some aspects, a pharmaceutical composition described herein can have a disintegration time of less than 20 minutes, less than 18 minutes, less than 16 minutes, less than 14 minutes, less than 12 minutes, less than 9 minutes, less than 7 minutes, or less than 5 minutes. [0424] In some aspects, a pharmaceutical composition described herein can have a hardness of from about 1 kilopond (kp) to about 60 kp. In some aspects, a pharmaceutical
composition described herein can have a hardness of from about 1 kp to about 5 kp, from about 1 kp to about 7.5 kp, from about 1 kp to about 10 kp, from about 1 kp to about 12.5 kp, from about 1 kp to about 15 kp, from about 1 kp to about 17.5 kp, from about 1 kp to about 20 kp, from about 1 kp to about 30 kp, from about 1 kp to about 40 kp, from about 1 kp to about 50 kp, from about 1 kp to about 60 kp, from about 5 kp to about 7.5 kp, from about 5 kp to about 10 kp, from about 5 kp to about 12.5 kp, from about 5 kp to about 15 kp, from about 5 kp to about 17.5 kp, from about 5 kp to about 20 kp, from about 5 kp to about 30 kp, from about 5 kp to about 40 kp, from about 5 kp to about 50 kp, from about 5 kp to about 60 kp, from about 10 kp to about 12.5 kp, from about 10 kp to about 15 kp, from about 10 kp to about 17.5 kp, from about 10 kp to about 20 kp, from about 10 kp to about 30 kp, from about 10 kp to about 40 kp, from about 10 kp to about 50 kp, from about 10 kp to about 60 kp, from about 12.5 kp to about 15 kp, from about 12.5 kp to about 17.5 kp, from about 12.5 kp to about 20 kp, from about 12.5 kp to about 30 kp, from about 12.5 kp to about 40 kp, from about 12.5 kp to about 50 kp, from about 12.5 kp to about 60 kp, from about 15 kp to about 17.5 kp, from about 15 kp to about 20 kp, from about 15 kp to about 30 kp, from about 15 kp to about 40 kp, from about 15 kp to about 50 kp, from about 15 kp to about 60 kp, from about 17.5 kp to about 20 kp, from about 17.5 kp to about 30 kp, from about 17.5 kp to about 40 kp, from about 17.5 kp to about 50 kp, from about 17.5 kp to about 60 kp, from about 20 kp to about 30 kp, from about 20 kp to about 40 kp, from about 20 kp to about 50 kp, from about 20 kp to about 60 kp, from about 30 kp to about 40 kp, from about 30 kp to about 50 kp, from about 30 kp to about 60 kp, from about 40 kp to about 50 kp, from about 40 kp to about 60 kp, or from about 50 kp to about 60 kp. [0425] In some aspects, a pharmaceutical composition described herein can have a hardness of about 10 kp. In some aspects, a pharmaceutical composition described herein can have a hardness of about 1 kp, about 2 kp, about 3 kp, about 4 kp, about 5 kp, about 6 kp, about 7 kp, about 8 kp, about 9 kp, about 10 kp, about 11 kp, about 12 kp, about 13 kp, about 14 kp, about 15 kp, about 16 kp, about 17 kp, about 18 kp, about 19 kp, about 20 kp, about 25 kp, about 30 kp, about 35 kp, about 40 kp, about 45 kp, about 50 kp, about 55 kp, or about 60 kp. [0426] In some aspects, a pharmaceutical composition described herein, when the pharmaceutical composition is administered to a subject with food, can provide a vamorolone Tmax of from about 0.5 hours to about 5 hours. In some aspects, a
pharmaceutical composition described herein, when the pharmaceutical composition is administered to a subject with food, can provide a vamorolone Tmax of from about 0.5 hours to about 1.5 hours, from about 0.5 hours to about 2.5 hours, from about 0.5 hours to about 3.5 hours, from about 0.5 hours to about 4.5 hours, from about 1.5 hours to about 2.5 hours, from about 1.5 hours to about 3.5 hours, from about 1.5 hours to about 4.5 hours, from about 1.5 hours to about 5 hours, from about 2.5 hours to about 3.5 hours, from about 2.5 hours to about 4.5 hours, from about 2.5 hours to about 5 hours, from about 3.5 hours to about 4.5 hours, from about 3.5 hours to about 5 hours, or from about 4.5 hours to about 5 hours. [0427] In some aspects, a pharmaceutical composition described herein, when the pharmaceutical composition is administered to a subject with food, can provide a vamorolone median Tmax of about 2 hours. In some aspects, a pharmaceutical composition described herein, when the pharmaceutical composition is administered to a subject with food, can provide a vamorolone median Tmax of about 0.5 hours, about 1 hour, about 1.5 hours, about 2 hours, about 2.5 hours, about 3 hours, about 3.5 hours, about 4 hours, about 4.5 hours, or about 5 hours. [0428] In some aspects, a pharmaceutical composition described herein, when the pharmaceutical composition is administered to a subject with food, can provide a vamorolone AUC24 of from about 2,600 ng∙h/mL to about 4,350 ng∙h/mL. In some aspects, a pharmaceutical composition described herein, when the pharmaceutical composition is administered to a subject with food, can provide a vamorolone AUC24 of from about 2,500 ng∙h/mL to about 3,000 ng∙h/mL, from about 2,500 ng∙h/mL to about 3,500 ng∙h/mL, from about 2,500 ng∙h/mL to about 4,000 ng∙h/mL, from about 2,500 ng∙h/mL to about 4,500 ng∙h/mL, from about 3,000 ng∙h/mL to about 3,500 ng∙h/mL, from about 3,000 ng∙h/mL to about 4,000 ng∙h/mL, from about 3,000 ng∙h/mL to about 4,500 ng∙h/mL, from about 3,500 ng∙h/mL to about 4,000 ng∙h/mL, from about 3,500 ng∙h/mL to about 4,500 ng∙h/mL, or from about 4,000 ng∙h/mL to about 4,500 ng∙h/mL. [0429] In some aspects, a pharmaceutical composition described herein, when the pharmaceutical composition is administered to a subject with food, can provide a vamorolone AUC24 of about 3,500 ng∙h/mL. In some aspects, a pharmaceutical composition described herein, when the pharmaceutical composition is administered to a subject with food, can provide a vamorolone AUC24 of about 2,500 ng∙h/mL, about 2,750
ng∙h/mL, about 3,000 ng∙h/mL, about 3,250 ng∙h/mL, about 3,500 ng∙h/mL, about 3,750 ng∙h/mL, about 4,000 ng∙h/mL, about 4,250 ng∙h/mL, or about 4,500 ng∙h/mL. [0430] In some aspects, a pharmaceutical composition described herein, when the pharmaceutical composition is administered to a subject with food, can provide a vamorolone Cmax of from about 650 ng/mL to about 1,200 mg/mL. In some aspects, a pharmaceutical composition described herein, when the pharmaceutical composition is administered to a subject with food, can provide a vamorolone Cmax of from about 600 ng/mL to about 700 mg/mL, from about 600 ng/mL to about 800 mg/mL, from about 600 ng/mL to about 900 mg/mL, from about 600 ng/mL to about 1,000 mg/mL, from about 600 ng/mL to about 1,100 mg/mL, from about 600 ng/mL to about 1,200 mg/mL, from about 700 ng/mL to about 800 mg/mL, from about 700 ng/mL to about 900 mg/mL, from about 700 ng/mL to about 1,000 mg/mL, from about 700 ng/mL to about 1,100 mg/mL, from about 700 ng/mL to about 1,200 mg/mL, from about 800 ng/mL to about 900 mg/mL, from about 800 ng/mL to about 1,000 mg/mL, from about 800 ng/mL to about 1,100 mg/mL, from about 800 ng/mL to about 1,200 mg/mL, from about 900 ng/mL to about 1,000 mg/mL, from about 900 ng/mL to about 1,100 mg/mL, from about 900 ng/mL to about 1,200 mg/mL, from about 1,000 ng/mL to about 1,100 mg/mL, from about 1,000 ng/mL to about 1,200 mg/mL, or from about 1,100 ng/mL to about 1,200 mg/mL. [0431] In some aspects, a pharmaceutical composition described herein, when the pharmaceutical composition is administered to a subject with food, can provide a vamorolone Cmax of from about 900 ng/mL. In some aspects, a pharmaceutical composition described herein, when the pharmaceutical composition is administered to a subject with food, can provide a vamorolone Cmax of from about 600 ng/mL, about 650 ng/mL, about 700 ng/mL, about 750 ng/mL, about 800 ng/mL, about 850 ng/mL, about 950 ng/mL, about 1,000 ng/mL, about 1,050 ng/mL, about 1,100 ng/mL, or about 1,200 ng/mL. [0432] In some aspects, the pharmaceutical composition described herein provides an AUC and/or Cmax that is bioequivalent to the AUC and/or Cmax achieved when a subject in need thereof is dosed with an equivalent amount of AGAMREE®. The term “bioequivalent” has the meaning defined in 21 C.F.R. § 320.1(e) and refers to the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at
the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study. In practice, two products are considered bioequivalent if the 90% confidence interval of the AUC or Cmax is within 80.00% to 125.00% relative to the reference product. Processes for Preparing Pharmaceutical Compositions [0433] The present disclosure also provides processes for preparing the pharmaceutical compositions disclosed herein, comprising: a) admixing vamorolone, a polymer, and optionally one or more of a plasticizer, a surfactant, or a filler, to form a mixture; b) extruding the mixture to form an amorphous solid dispersion; c) pelletizing or milling the amorphous solid dispersion; and d) admixing the amorphous solid dispersion with one or more pharmaceutically acceptable excipients. [0434] The present disclosure also provides processes for preparing the pharmaceutical compositions disclosed herein, comprising: a) admixing vamorolone, a polymer, and an organic solvent to form a mixture; b) spray drying the mixture to form an amorphous solid dispersion; and c) admixing the amorphous solid dispersion with one or more pharmaceutically acceptable excipients. [0435] The present disclosure also provides processes for preparing the pharmaceutical compositions disclosed herein, comprising admixing crystalline vamorolone with one or more pharmaceutically acceptable excipients. [0436] The pharmaceutical compositions disclosed herein can, in some embodiments, be prepared using the following equipment. [0437] In some aspects, powders used to prepare a pharmaceutical composition disclosed herein can be mixed using a V-blender (with or without an intensifier bar), a ribbon blender, a bin-blender, a TURBULA® mixer, a planetary mixer, or a high-shear mixer. [0438] In some aspects, a pharmaceutical composition disclosed herein can be prepared by wet granulation using a high shear granulator, a planetary mixer, or a V-blender with liquid injection and an intensifier bar.
[0439] In some aspects, a pharmaceutical composition disclosed herein can milled using a DYNO®-MILL, a hammer mill (e.g., FITZMILL™), a ball mill, a screen mill (e.g., a co- mill or Fitzpatrick oscillating generator), or a jet mill. [0440] In some aspects, a pharmaceutical composition disclosed herein is prepared using a fluid bed granulator, which can be any size. In some aspects, the fluid bed granulator is a top spray fluid bed granulator, a bottom spray fluid bed granulator (Wurster column), or a tangential spray (rotor insert) fluid bed granulator. [0441] In some aspects, a process for preparing a pharmaceutical composition disclosed herein comprises drying powders. In some aspects, powders can be dried using a tray dry oven, a fluid bed dryer, a rotary drum dryer, an air dryer, a tunnel dryer, or a heat jacket high shear granulator. [0442] In some aspects wherein a pharmaceutical composition disclosed herein is a tablet, the tablet can be coated. In some aspects, the tablet can be coated using an unperforated coating pan, a perforated coating pan, or a fluid bed coating. [0443] In some aspects, a process for preparing a pharmaceutical composition disclosed herein comprises mixing liquids. In some aspects, liquids can be mixed using tanks having a high shear mixing head, an impeller mixer (e.g., a LIGHTNIN® mixer), a homogenization head, and/or slow speed paddles. In some aspects, the tank can be a closed tank having an inert atmosphere. In some aspects, the tank can be heated or cooled. [0444] In some aspects, a process for preparing a pharmaceutical composition disclosed herein comprises spray drying. Spray drying can be performed using any size spray dryer. [0445] In some aspects, a process for preparing a pharmaceutical composition disclosed herein comprises extruding a mixture. In some aspects, the extruding can be performed in a single screw extruder, a twin screw extruder, a hot melt extruder, or a extruder- spheronizer. [0446] In some aspects, a process for preparing a pharmaceutical composition disclosed herein comprises compressing a mixture to form a tablet using a tablet press. In some aspects, the tablet press can be a single station, a rotary press (e.g., 8 to 71 stations), a compaction simulator, or a tablet deduster. [0447] In some aspects, a process for preparing a pharmaceutical composition disclosed herein comprises encapsulating a mixture using an encapsulator. In some aspects, the encapsulator can be a manual fill apparatus (e.g., PROFILLER®), a semi-automatic capsule filler (e.g., PD-10), XCELODOSE®, or an automatic encapsulator.
[0448] In some aspects, process for preparing a pharmaceutical composition disclosed herein comprises particle size sieving. In some aspects, sieving can be performed using a manual hand screen or a motorized screen sifter (e.g., a SWECO® sifter). [0449] In some aspects, process for preparing a pharmaceutical composition disclosed herein comprises moving a liquid. In some aspects, a liquid can be moved using a centrifugal pump or a peristatic pump. [0450] In some aspects, process for preparing a pharmaceutical composition disclosed herein comprises moving a powder. In some aspects, a powder can be moved manually, e.g., in drums, by a gravity feed between equipment, by a vacuum transfer, or by a conveyor. [0451] In some aspects, process for preparing a pharmaceutical composition disclosed herein comprises granulation densification. In some aspects, granulation densification can be performed using a roller compactor, by slugging (i.e., preparing large tablets or “slugs”) with a tablet press, or by using a lentiling machine. Methods of Treatment [0452] In certain embodiments, the present disclosure also provides a method of treating muscular dystrophy in a subject in need thereof, comprising orally administering any of the pharmaceutical compositions disclosed herein to the subject. [0453] In some aspects, the pharmaceutical composition can be administered 1, 2, 3, 4, 5, 6, 7, or 8 times per day. In some aspects, the pharmaceutical composition can be administered once per day. In some aspects, the pharmaceutical composition can be administered twice per day. In some aspects, the pharmaceutical composition can be administered 3 times per day. In some aspects, the pharmaceutical composition can be administered 4 times per day. In some aspects, the pharmaceutical composition can be administered 5 times per day. In some aspects, the pharmaceutical composition can be administered 6 times per day. In some aspects, the pharmaceutical composition can be administered 7 times per day. In some aspects, the pharmaceutical composition can be administered 8 times per day. [0454] In some aspects, the pharmaceutical composition can be administered with food. In some aspects, the pharmaceutical composition can be administered without food.
[0455] In some aspects, the pharmaceutical composition can be administered 1, 2, 3, 4, 5, 6, 7, or 8 times per day with food. In some aspects, the pharmaceutical composition can be administered 1, 2, 3, 4, 5, 6, 7, or 8 times per day without food. [0456] In some aspects, the muscular dystrophy can be Duchenne muscular dystrophy, Becker muscular dystrophy, limb girdle muscular dystrophy, congenital muscular dystrophy, facioscapulohumeral muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, distal muscular dystrophy, or Emery-Dreifuss muscular dystrophy. [0457] In some aspects, the muscular dystrophy can be Duchenne muscular dystrophy. [0458] In some aspects, the muscular dystrophy can be Duchenne muscular dystrophy and the pharmaceutical composition can be administered 1, 2, 3, 4, 5, 6, 7, or 8 times per day with food. In some aspects, the muscular dystrophy can be Duchenne muscular dystrophy and the pharmaceutical composition can be administered 1, 2, 3, 4, 5, 6, 7, or 8 times per day without food. [0459] In some aspects, a total daily dose of vamorolone of from about 2 mg/kg to about 6 mg/kg can be administered to the subject in the form of any of the pharmaceutical compositions described herein. In some aspects, a total daily dose of vamorolone of from about 2 mg/kg to about 3 mg/kg, from about 2 mg/kg to about 4 mg/kg, from about 2 mg/kg to about 5 mg/kg, from about 3 mg/kg to about 4 mg/kg, from about 3 mg/kg to about 5 mg/kg, from about 3 mg/kg to about 6 mg/kg, from about 4 mg/kg to about 5 mg/kg, from about 4 mg/kg to about 6 mg/kg, or from about 5 mg/kg to about 6 mg/kg can be administered to the subject in the form of any of the pharmaceutical compositions described herein. [0460] In some aspects, a total daily dose of vamorolone of about 6 mg/kg can be administered to the subject in the form of any of the pharmaceutical compositions described herein. In some aspects, a total daily dose of vamorolone of about 2 mg/kg, about 3 mg/kg, about 4 mg/kg, or about 5 mg/kg can be administered to the subject in the form of any of the pharmaceutical compositions described herein. [0461] In some aspects, a total daily dose of vamorolone of from about 2 mg/kg to about 3 mg/kg, from about 2 mg/kg to about 4 mg/kg, from about 2 mg/kg to about 5 mg/kg, from about 3 mg/kg to about 4 mg/kg, from about 3 mg/kg to about 5 mg/kg, from about 3 mg/kg to about 6 mg/kg, from about 4 mg/kg to about 5 mg/kg, from about 4 mg/kg to about 6 mg/kg, or from about 5 mg/kg to about 6 mg/kg can be administered to the
subject in the form of any of the pharmaceutical compositions described herein as a series of 1, 2, 3, 4, 5, 6, 7, or 8 doses. [0462] In some aspects, a total daily dose of vamorolone of about 6 mg/kg can be administered to the subject. In some aspects, a total daily dose of vamorolone of about 2 mg/kg, about 3 mg/kg, about 4 mg/kg, or about 5 mg/kg can be administered to the subject as a series of 1, 2, 3, 4, 5, 6, 7, or 8 doses of the pharmaceutical composition. [0463] In some aspects, a total daily dose of vamorolone of from about 25 mg to about 50 mg, from about 25 mg to about 75 mg, from about 25 mg to about 100 mg, from about 25 mg to about 125 mg, from about 25 mg to about 150 mg, from about 25 mg to about 175 mg, from about 25 mg to about 200 mg, from about 25 mg to about 225 mg, from about 25 mg to about 250 mg, from about 25 mg to about 275 mg, from about 25 mg to about 300 mg, from about 50 mg to about 75 mg, from about 50 mg to about 100 mg, from about 50 mg to about 125 mg, from about 50 mg to about 150 mg, from about 50 mg to about 175 mg, from about 50 mg to about 200 mg, from about 50 mg to about 225 mg, from about 50 mg to about 250 mg, from about 50 mg to about 275 mg, from about 50 mg to about 300 mg, from about 75 mg to about 100 mg, from about 75 mg to about 125 mg, from about 75 mg to about 150 mg, from about 75 mg to about 175 mg, from about 75 mg to about 200 mg, from about 75 mg to about 225 mg, from about 75 mg to about 250 mg, from about 75 mg to about 275 mg, from about 75 mg to about 300 mg, from about 100 mg to about 125 mg, from about 100 mg to about 150 mg, from about 100 mg to about 175 mg, from about 100 mg to about 200 mg, from about 100 mg to about 225 mg, from about 100 mg to about 250 mg, from about 100 mg to about 275 mg, from about 100 mg to about 300 mg, from about 125 mg to about 150 mg, from about 125 mg to about 175 mg, from about 125 mg to about 200 mg, from about 125 mg to about 225 mg, from about 125 mg to about 250 mg, from about 125 mg to about 275 mg, from about 125 mg to about 300 mg, from about 150 mg to about 175 mg, from about 150 mg to about 200 mg, from about 150 mg to about 225 mg, from about 150 mg to about 250 mg, from about 150 mg to about 275 mg, from about 150 mg to about 300 mg, from about 175 mg to about 200 mg, from about 175 mg to about 225 mg, from about 175 mg to about 250 mg, from about 175 mg to about 275 mg, from about 175 mg to about 300 mg, from about 200 mg to about 225 mg, from about 200 mg to about 250 mg, from about 200 mg to about 275 mg, from about 200 mg to about 300 mg, from about 225 mg to about 250 mg, from about 225 mg to about 275 mg, from about 225 mg to about 300
mg, from about 250 mg to about 275 mg, from about 250 mg to about 300 mg, or from about 275 mg to about 300 mg can be administered to the subject in the form of any of the pharmaceutical compositions described herein. [0464] In some aspects, a total daily dose of vamorolone of about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, or about 300 mg can be administered to the subject in the form of any of the pharmaceutical compositions described herein. [0465] In some aspects, a total daily dose of vamorolone of from about 25 mg to about 50 mg, from about 25 mg to about 75 mg, from about 25 mg to about 100 mg, from about 25 mg to about 125 mg, from about 25 mg to about 150 mg, from about 25 mg to about 175 mg, from about 25 mg to about 200 mg, from about 25 mg to about 225 mg, from about 25 mg to about 250 mg, from about 25 mg to about 275 mg, from about 25 mg to about 300 mg, from about 50 mg to about 75 mg, from about 50 mg to about 100 mg, from about 50 mg to about 125 mg, from about 50 mg to about 150 mg, from about 50 mg to about 175 mg, from about 50 mg to about 200 mg, from about 50 mg to about 225 mg, from about 50 mg to about 250 mg, from about 50 mg to about 275 mg, from about 50 mg to about 300 mg, from about 75 mg to about 100 mg, from about 75 mg to about 125 mg, from about 75 mg to about 150 mg, from about 75 mg to about 175 mg, from about 75 mg to about 200 mg, from about 75 mg to about 225 mg, from about 75 mg to about 250 mg, from about 75 mg to about 275 mg, from about 75 mg to about 300 mg, from about 100 mg to about 125 mg, from about 100 mg to about 150 mg, from about 100 mg to about 175 mg, from about 100 mg to about 200 mg, from about 100 mg to about 225 mg, from about 100 mg to about 250 mg, from about 100 mg to about 275 mg, from about 100 mg to about 300 mg, from about 125 mg to about 150 mg, from about 125 mg to about 175 mg, from about 125 mg to about 200 mg, from about 125 mg to about 225 mg, from about 125 mg to about 250 mg, from about 125 mg to about 275 mg, from about 125 mg to about 300 mg, from about 150 mg to about 175 mg, from about 150 mg to about 200 mg, from about 150 mg to about 225 mg, from about 150 mg to about 250 mg, from about 150 mg to about 275 mg, from about 150 mg to about 300 mg, from about 175 mg to about 200 mg, from about 175 mg to about 225 mg, from about 175 mg to about 250 mg, from about 175 mg to about 275 mg, from about 175 mg to about 300 mg, from about 200 mg to about 225 mg, from about 200 mg to about 250 mg, from about 200 mg to about 275 mg, from about 200 mg to about 300 mg, from about 225 mg
to about 250 mg, from about 225 mg to about 275 mg, from about 225 mg to about 300 mg, from about 250 mg to about 275 mg, from about 250 mg to about 300 mg, or from about 275 mg to about 300 mg can be administered to the subject as a series of 1, 2, 3, 4, 5, 6, 7, or 8 doses in the form of any of the pharmaceutical compositions described herein. [0466] In some aspects, a total daily dose of vamorolone of about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, or about 300 mg can be administered to the subject as a series of 1, 2, 3, 4, 5, 6, 7, or 8 doses in the form of any of the pharmaceutical compositions described herein. [0467] In some aspects, a dose of vamorolone of from about 5 mg to about 10 mg, from about 5 mg to about 20 mg, from about 5 mg to about 30 mg, from about 5 mg to about 40 mg, from about 5 mg to about 50 mg, from about 5 mg to about 60 mg, from about 5 mg to about 70 mg, from about 5 mg to about 80 mg, from about 5 mg to about 90 mg, from about 5 mg to about 100 mg, from about 10 mg to about 20 mg, from about 10 mg to about 30 mg, from about 10 mg to about 40 mg, from about 10 mg to about 50 mg, from about 10 mg to about 60 mg, from about 10 mg to about 70 mg, from about 10 mg to about 80 mg, from about 10 mg to about 90 mg, from about 10 mg to about 100 mg, from about 20 mg to about 30 mg, from about 20 mg to about 40 mg, from about 20 mg to about 50 mg, from about 20 mg to about 60 mg, from about 20 mg to about 70 mg, from about 20 mg to about 80 mg, from about 20 mg to about 90 mg, from about 20 mg to about 100 mg, from about 30 mg to about 40 mg, from about 30 mg to about 50 mg, from about 30 mg to about 60 mg, from about 30 mg to about 70 mg, from about 30 mg to about 80 mg, from about 30 mg to about 90 mg, from about 30 mg to about 100 mg, from about 40 mg to about 50 mg, from about 40 mg to about 60 mg, from about 40 mg to about 70 mg, from about 40 mg to about 80 mg, from about 40 mg to about 90 mg, from about 40 mg to about 100 mg, from about 50 mg to about 60 mg, from about 50 mg to about 70 mg, from about 50 mg to about 80 mg, from about 50 mg to about 90 mg, from about 50 mg to about 100 mg, from about 60 mg to about 70 mg, from about 60 mg to about 80 mg, from about 60 mg to about 90 mg, from about 60 mg to about 100 mg, from about 70 mg to about 80 mg, from about 70 mg to about 90 mg, from about 70 mg to about 100 mg, from about 80 mg to about 90 mg, from about 80 mg to about 100 mg, or from about 90 mg to about 100 mg can be administered to the subject 1, 2, 3, 4, 5, 6, 7,
or 8 times per day in the form of any of the pharmaceutical compositions described herein. [0468] In some aspects, a dose of vamorolone of about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, or about 100 mg can be administered to the subject 1, 2, 3, 4, 5, 6, 7, or 8 times per day in the form of any of the pharmaceutical compositions described herein. [0469] In some aspects, the subject is at least two years of age. In some aspects, the subject is a child. In some aspects, the subject is an adult. As used herein, the term “child” refers to a human subject who is under the age of 18. As used herein, the term “adult” refers to a human subject who is 18 years of age or older. [0470] In some aspects, the muscular dystrophy can be Duchenne muscular dystrophy and a total daily dose of vamorolone of from about 2 mg/kg to about 3 mg/kg, from about 2 mg/kg to about 4 mg/kg, from about 2 mg/kg to about 5 mg/kg, from about 3 mg/kg to about 4 mg/kg, from about 3 mg/kg to about 5 mg/kg, from about 3 mg/kg to about 6 mg/kg, from about 4 mg/kg to about 5 mg/kg, from about 4 mg/kg to about 6 mg/kg, or from about 5 mg/kg to about 6 mg/kg can be administered to the subject as a series of 1, 2, 3, 4, 5, 6, 7, or 8 doses in the form of any of the pharmaceutical compositions described herein. [0471] In some aspects, the muscular dystrophy can be Duchenne muscular dystrophy and a dose of vamorolone of from about 5 mg to about 10 mg, from about 5 mg to about 20 mg, from about 5 mg to about 30 mg, from about 5 mg to about 40 mg, from about 5 mg to about 50 mg, from about 5 mg to about 60 mg, from about 5 mg to about 70 mg, from about 5 mg to about 80 mg, from about 5 mg to about 90 mg, from about 5 mg to about 100 mg, from about 10 mg to about 20 mg, from about 10 mg to about 30 mg, from about 10 mg to about 40 mg, from about 10 mg to about 50 mg, from about 10 mg to about 60 mg, from about 10 mg to about 70 mg, from about 10 mg to about 80 mg, from about 10 mg to about 90 mg, from about 10 mg to about 100 mg, from about 20 mg to about 30 mg, from about 20 mg to about 40 mg, from about 20 mg to about 50 mg, from about 20 mg to about 60 mg, from about 20 mg to about 70 mg, from about 20 mg to about 80 mg, from about 20 mg to about 90 mg, from about 20 mg to about 100 mg, from about 30 mg to about 40 mg, from about 30 mg to about 50 mg, from about 30 mg to
about 60 mg, from about 30 mg to about 70 mg, from about 30 mg to about 80 mg, from about 30 mg to about 90 mg, from about 30 mg to about 100 mg, from about 40 mg to about 50 mg, from about 40 mg to about 60 mg, from about 40 mg to about 70 mg, from about 40 mg to about 80 mg, from about 40 mg to about 90 mg, from about 40 mg to about 100 mg, from about 50 mg to about 60 mg, from about 50 mg to about 70 mg, from about 50 mg to about 80 mg, from about 50 mg to about 90 mg, from about 50 mg to about 100 mg, from about 60 mg to about 70 mg, from about 60 mg to about 80 mg, from about 60 mg to about 90 mg, from about 60 mg to about 100 mg, from about 70 mg to about 80 mg, from about 70 mg to about 90 mg, from about 70 mg to about 100 mg, from about 80 mg to about 90 mg, from about 80 mg to about 100 mg, or from about 90 mg to about 100 mg can be administered to the subject 1, 2, 3, 4, 5, 6, 7, or 8 times per day in the form of any of the pharmaceutical compositions described herein. EXAMPLES [0472] The examples presented below are provided for the purpose of illustration only and the embodiments described herein should in no way be construed as limiting to these examples. Rather, the embodiments should be construed to encompass any and all variations which become evident as a result of the teaching provided herein. General Procedures X-Ray Powder Diffraction (XRPD) [0473] XRPD was conducted using one of the methods described below. [0474] XRPD Method 1: XRPD analyses were conducted on a BRUKER® AXS D8 Advance DaVinci model system with a Bragg-Brentano configuration using CuKα radiation and Lynx-Eye silicon strip detector. Samples were typically analyzed at room temperature using the following method parameters: power setting of 40 kV, 40 mA, 0.6mm divergence and 18mm anti-scatter slits, 2.5° soller slits, coupled two Θ/Θ, continuous mode from 2 – 40°2Θ with a 0.05° step size, 1 second/step rate, and 15rpm rotation speed. Approximately 400 mg of sample was required for analysis using a top- filled steel sample holder. [0475] XRPD Method 2: XRPD diffractograms were acquired on RIGAKU® X-Ray Powder Diffractometer MiniFlex 600 FAE-R at the following parameters: Soller (inc.)
5.0 deg, IHS 10.0 mm, SS 1.250 deg, DS 1.250 deg, Soller (rec) 5.0 deg, RS 0.3 mm, Scan Axis Theta/2-Theta, Mode Continuous, Start (deg) 2.0, Stop (deg) 40.0, Step (deg) 0.020, Speed (deg/min) 2.5, Spin-yes, Voltage (kV) 30, Current (mA) 15. Samples were mounted flat on zero-background Si wafers. [0476] XRPD Method 3: XRPD diffractograms were acquired using the parameters listed in Table 1 below. Table 1
Differential Scanning Calorimetry (DSC) [0477] DSC was conducted using one of the methods described below. [0478] DSC Method 1: DSC analyses were conducted on a TA Instruments Discovery series 2500 DSC. Approximately 5-10 mg samples was required for analysis in a closed Tzero aluminum DSC pan, using a ramp rate of 10°C/minute from 25°C to 300°C and a 50 cc/minute nitrogen purge flow. [0479] DSC Method 2: DSC was conducted using a TA Instruments Discovery model 2500 differential scanning calorimeter equipped with an autosampler and a refrigerated cooling system under 50 mL/min N2 purge. DSC thermograms were obtained using a linear ramp rate with or without modulation. Standard modulation was +/- 1°C every 60 seconds with a sample interval of 2.0s/pt, and a ramp 3.00°C/min to 200 °C (or other maximum based on thermal degradation). Sample preparation was in standard Tzero pans or as otherwise stated. [0480] DSC Method 3: DSC was conducted using the parameters described in Table 2.
Table 2
Non-Sink Dissolution Testing [0481] Non-sink dissolution testing was conducted using one of the methods described below. [0482] Non-Sink Dissolution Test Method 1: Non-sink dissolution performance was evaluated using a two-stage transfer (SGF-FaSSIF) dissolution test with a 1:1 transfer ratio. The concentration of Vamorolone was quantitated using PION fiber optic UV-Vis probes. All probes were calibrated in the same standard solution of known concentration (~0.033mg/mL) to give a response factor (RF). The RF (Abs/conc.) of each probe was used to calculate each sample measured by that probe as follows: % Released = (Sample Abs/RF) x ((media volume)/(label claim)) x 100. The dissolution bath and fiber optic parameters are shown in Table 3. Table 3
[0483] The dissolution tests were conducted in duplicate at a 600 μg/mL dose concentration in SGF and a 300 μg/mL dose concentration in FaSSIF. PION
quantification was performed using the second derivative of the spectra with a quantitation λ range between 288 and 298 nm. The media composition is shown below in Table 4. Table 4
[0484] Non-Sink Dissolution Test Method 2: Dissolution behavior was measured using the parameters listed in Table 5. Table 5
[0485] Sample in a vial was wetted with gastic media and vortexed for 10 s, then emptied into a vessel containing 0.01 N HCl media. The vial was rinsed with additional media, vortexed for 10 s, and emptied into the vessel. After 30 minutes, the media was modulated from gastric media (SGF) to intestinal media (FaSSIF) by adding an equivalent volume of 2X FaSSIF. At each timepoint, an aliquot was centrifuged to pellet undissolved material, and the supernatant was diluted and analyzed by HPLC. [0486] Non-Sink Dissolution Test Method 3: Dissolution behavior was measured using the parameters listed in Table 5-A below. Samples were analyzed using HPLC. Table 5-A
Tablet Characteristics [0487] The disintegration, hardness and thickness, and compressibility of tablets were tested using the following procedures. [0488] Disintegration: Disintegration testing was performued using an automated disintegration apparatus produced by Agilent. The water bath of the apparatus was heated to 37 °C to simulate gastric temperature. The tablets were placed into a basket containing 6 separate cylinders with a perforated bottom to allow water to pass through. A perforated sinker was also placed on top of the tablets to prevent them from floating. The baskets were submerged into the water bath and moved up and down. The time at which all tablets completely disintegrated was recorded as the disintegration time. [0489] Hardness/Thickness: Tablet hardness and thickness were measured using a Dr. Schleuniger multi-tester. Each tablet was measured individually. [0490] Compressibility: Compressibility was evaluated during the single station compression phase of tablet production. Compaction force and ejection force were measured to determine the compressibility of a given blend. Example 1: Vamorolone Amorphous Solid Dispersions Prepared by Hot Melt Extrusion [0491] Crystalline vamorolone, a polymer, and, optionally, a plasticizer and/or a surfactant are fed into an extruder and are processed at a pressure and temperature sufficient to melt the material and to convert the crystalline vamorolone into an amorphous vamorolone immobilized within a stable polymer system. The materials described above are blended, heated, mixed, and pumped into the extruder. After extrusion, the extrudate is pelletized or milled to acceptably sized granules. An in-line pelletizer or suitable mill (FitzMill, comil) is used. The pellets and/or granules are used as-is (i.e. encapsulated, put into sachets or stick packs, bottled for re-suspension) or are processed further, as described in Examples 6 and 7. Exemplary blends suitable for hot- melt extrusion to prepare amorphous solid dispersions are shown in Table 6.
Table 6
Example 1a: Evaluation of Feasibility of Polymers for Preparing Vamorolone Amorphous Solid Dispersions by Hot Melt Extrusion [0492] The feasibility of using hot melt extrusion to prepare vamorolone amorphous solid dispersions with various polymers was studied, and the upper bound of drug loading for each polymer system was determined. [0493] Pre-formulation screening studies were conducted to evaluate the miscibility of vamorolone in various polymers suitable for HME. Due to the high melting point of vamorolone (about 250 °C), polymers with relatively high processing temperatures were prioritized (PVP VA64, SOLUPLUS®, PVA 4-88 and HPMCAS). DSC and hot stage microscopy were used to evaluate miscibility/solubility at various drug loadings. The drug-polymer phase diagrams shown in FIGS.9-12 were prepared based on these data. These diagrams indicate the approximate processing windows for each system. The upper processing temperature is bounded by the degradation temperature of the polymer, whereas the lower processing temperature is bounded by the solubility temperature. Example 1b: Vamorolone Amorphous Solid Dispersions Prepared by Hot Melt Extrusion [0494] Vamorolone amorphous solid dispersions were prepared using hot melt extrusion. Hot melt extrusion was performed at temperatures ranging from 195 °C to 220 °C. The hot melt extrudates (HMEs) were analyzed by X-ray powder diffraction (XRPD) to determine whether crystalline vamorolone was present. The formulations and their morphology as determined by XRPD are shown in Table 7. Table 7
[0495] The dissolution behavior of loose HME granules was measured using Non-Sink Dissolution Test 1. [0496] FIG.13 shows the impact of solubilizer concentration (5% vs 10% Labrosol) on drug release compared to an oral suspension of vamorolone. [0497] FIG.14 shows the effect of drug loading (DL) on drug release in loose HME granules comprising PVP K30 compared to an oral suspension of vamorolone. The 10% DL sample went to 140% final release, likely due to a uniformity issue, so the data were normalized. [0498] FIG.15 shows drug release for loose HME granules comprising different polymers. PVP K30 had the fastest release rate of the polymers studied. Loose HME granules comprising EUDRAGIT® E (not shown in figure) exhibited a slow release rate with only 67% final release. [0499] Hot melt extrudates comprising PVP K30 were further investigated. Hot melt extrudates comprising PVP K30 and 30-50% vamorolone were prepared and characterized by XRPD, as shown in Table 8. Table 8
Example 1c: Additional Vamorolone Amorphous Solid Dispersions Prepared by Hot Melt Extrusion [0500] Vamorolone amorphous solid dispersions were prepared using hot melt extrusion. Vamorolone and the appropriate polymer were blended in a turbula blender for about 5 minutes, then de-lumped with #20 mesh and blended again for about 5 minutes. The mixture was then extruded using a HAAKE™ Mini CTW Extruder with a counter- rotating screw configuration, using a screw speed of about 100 rpm and target temperature of about 10 °C lower than the degradation temperature for the mixture. A force feeder was used to fill barrels. A single pass was made through the extruder. If the extruded material was not transparent, the material was recycled in the barrel for an additional 2 minutes and extruded. The extrudates were grinded using a tube mill and passed through #60 mesh. The solid dispersions prepared are listed in Table 9. The net weight of pellets obtained from 50 g of blend are shown in Tables 10 and 11. Table 9
Table 10
Table 11
XRPD [0501] The hot melt extrudates (HMEs) were analyzed by XRPD using XRPD Method 3. Intermediate Formulation 77 (10:90 vamorolone:PVA) and Intermediate Formulations 79 and 80 (vamorolone:SOLUPLUS®) were amorphous by XRPD, while all other HMEs had crystalline diffraction peaks aligning with vamorolone.
DSC [0502] The formulations were also characterized by DSC using DSC Method 3. The results are shown in Table 12. Table 12
ND = Not Detected; NA = Not Applicable [0503] Single Tgs were detected for the formulations comprising 10% Vamorolone in HPMC HP-55, PVA, and SOLUPLUS®; 10:80:10 Vamorolone:PVA:TPGS; 10:80:10 Vamorolone:HPMC HP-55:PEG6000; 10:80:10 Vamorolone:HPMC HP-55:TPGS; and 10:80:10 Vamorolone:HPMC HP-55:KOLLIPHOR® P188. A Tg was not observed in the formulation comprising 10:80:10 Vamorolone:PVA:PEG6000, most likely due to the PEG melt at 58 °C obscuring the Tg. A Tg was not observed for the formulation comprising 10:80:10 Vamorolone:PVA:KOLLIPHOR® P188, most likely due to the KOLLIPHOR® P188 melt at 53 °C obscuring the Tg. A TPGS melt was observed in the formulation comprising 10:80:10 Vamorolone:PVA:TPGS. The formulations comprising HPMC did not have TPGS, KOLLIPHOR® P188, or PEG6000 melts.
Scanning Electron Microscopy (SEM) [0504] The solid dispersions were also characterized by SEM using a Phenom XL2 instrument. [0505] Surface roughness was observed in the 10:90 Vamorolone:HPMC HP-55 HME, likely indicating crystallinity. Milled blocky particles were observed for 10% Vamorolone in PVA and SOLUPLUS® HMEs, with no surface roughness or crystallinity observed. [0506] Surface roughness was observed on 30:70 Vamorolone:SOLUPLUS® HME and 10:80:10 Vamorolone:PVA:PEG6000 HME, likely indicating crystallinity.10:80:10 Vamorolone:PVA:TPGS HME had a porous surface and did not appear to have crystallinity. [0507] The surface roughness observed in the SEM images of 10:80:10 Vamorolone:PVA:KOLLIPHOR® P188 HME, 10:80:10 Vamorolone:HPMC HP- 55:PEG6000 HME, 10:80:10 Vamorolone:HPMC HP-55:TPGS HME, and 10:80:10 Vamorolone:HPMC HP-55:KOLLIPHOR® P188 HME indicated the presence of crystalline vamorolone. Non-Sink Dissolution in Biorelevant Media [0508] The dissolution behavior of the solid dispersions was measured using Non-Sink Dissolution Method 3. The results are shown in Table 13. Table 13
[0509] All HMEs exhibited increased dissolution relative to crystalline vamorolone. Example 2: Vamorolone Amorphous Solid Dispersions Prepared by Twin-Screw Melt Granulation [0510] Crystalline vamorolone and a polymer are fed into a twin-screw extruder and processed under a pressure and temperature. The initial materials described above are pre- blended and fed as a single uniform mixture or are added individually into the twin-screw extruder. After extrusion, the extrudate is pelletized or milled to acceptably sized granules. An in-line pelletizer or suitable mill (FitzMill, comil) is used. The pellets and/or granules are used as-is (i.e. encapsulated, put into sachets or stick packs, bottled for re- suspension) or are processed further, as described in Examples 6 and 7. Exemplary blends suitable for twin-screw melt granulation to prepare amorphous solid dispersions are shown in Table 14. Table 14
Example 3: Vamorolone Amorphous Solid Dispersions Prepared by High Shear Melt Granulation [0511] Crystalline vamorolone, a polymer, and, optionally, a filler are loaded into a jacketed high shear granulator. The materials are mixed at a speed and temperature sufficient to melt the polymer and to dissolve the crystalline vamorolone into the melted polymer, thus converting it to the amorphous state. At the end of the granulation process, granules formed in the granulator are cooled back to the solid state. Once cool, the granules are optionally screened (vibratory sifter) and/or milled (Fitz-mill/comil). The granules are used as-is (i.e. encapsulated, put into sachets or stick packs, bottled for re- suspension) or are processed further, as described in Examples 6 and 7. Exemplary blends suitable for high shear melt granulation to prepare amorphous solid dispersions are shown in Table 15. Table 15
Example 4: Vamorolone Amorphous Solid Dispersions Prepared by Spray Drying [0512] Crystalline vamorolone and a polymer are dissolved into an organic solvent. The solution is atomized through a nozzle to produce atomized droplets, which are instantaneously dried in a high temperature gas stream yielding spray-dried granules. The spray-dried granules are used as-is (i.e. encapsulated, put into sachets or stick packs, bottled for re-suspension) or are processed further, as described in Examples 6 and 7. Exemplary blends suitable for spray drying to prepare amorphous solid dispersions are shown in Table 16. Table 16
Example 4a: Vamorolone Amorphous Solid Dispersions Prepared by Spray Drying [0513] Vamorolone amorphous solid dispersions were prepared by spray drying using the procedure described below. Spray Solution Preparation [0514] A 100-mL duran was tared on a top loading balance. A spray solvent solution (either 80:20 dichloromethane:methanol or 100% methanol) was added to the duran. The solution was transferred to a stir plate and mixed at the highest speed possible to create a medium vortex that did not aerate the solution. Once a vortex formed, an appropriate quantity of vamorolone was slowly added to the solution, and the solution was mixed
until all vamorolone dissolved. An appropriate quantity of polymer was then slowly added to the solution, which was mixed until the polymer dissolved. Spray Drying [0515] Spray dried dispersions (SDDs) were prepared using a ProCept 4M8-TriX equipped with a 0.6 mm 2-fluid nozzle. The system was conditioned with an outlet temperature of 70 °C, an inlet gas flow of 0.35 m3/min, a pump speed of 60 RPM, and a nozzle gas pressure of 0.30 bar. An 80:20 (v/v) dichloromethane/methanol wash solvent was sprayed until steady-state conditions were achieved, with the outlet temperature equilibrating at 41^°C. The feed was then switched to the active spray solution, which was sprayed until fully consumed. Following spray completion, the system was rinsed with the neat wash solvent. The resulting SDD was collected, and the collection vessel was replaced with a clean container. The system was then re-equilibrated to steady-state conditions prior to processing the next batch. [0516] The wet solids obtained from spray drying were dried in an oven at about 40 °C under nitrogen for at least about 16 hours. [0517] The SDDs prepared using this procedure are listed in Table 17. Table 17
XRPD and DSC [0518] The spray dried solid dispersions listed in Table 17 were analyzed by XRPD using XRPD Method 2 and DSC using DSC Method 2 to determine whether the solid dispersions were crystalline or amorphous. [0519] XRPD and DSC indicated that formulations comprising HPMCAS-H were amorphous at a vamorolone loading of 25% (Formulation IF96) and crystalline at vamorolone loadings of 50% and 75% (Formulations IF99 and IF102). [0520] XRPD and DSC indicated that formulations comprising SOLUPLUS® were crystalline at vamorolone loadings 25%, 50%, and 75% (Formulations IF947, IF100, and IF103). [0521] XRPD and DSC indicated that formulations comprising EUDRAGIT® L100 were amorphous at a vamorolone loading of 25% (Formulation IF98) and crystalline at vamorolone loadings of 50% and 75% (Formulations IF101 and IF104). [0522] XRPD and DSC indicated that formulations comprising EUDRAGIT® L100-55 (Formulations IF105, IF109, and IF113) show minor crystallinity, as well as phase separation in the 25% vamorolone sample. [0523] XRPD and DSC indicated that formulations comprising CAP were amorphous at vamorolone loadings of 25% and 50% (Formulations IF106 and IF110) and crystalline at a vamorolone loading 75% (Formulation IF114). [0524] XRPD and DSC indicated that formulations comprising PAA were amorphous at a vamorolone loading of 25% (Formulation IF107) and crystalline at vamorolone loadings of 50% and 75% (Formulations IF111 and IF115). [0525] XRPD and DSC indicated that formulations comprising APINOVEX™ LV phase separate and are crystalline.
Non-Sink Dissolution Tests [0526] Non-sink dissolution tests were conducted using Non-Sink Dissolution Test Method 1. Concentration timepoints, as well as FaSSIF AUC calculations and relative FaSSIF AUC compared to micronized vamorolone and a 4% w/w suspension of vamorolone (AGAMREE® are listed below in Table 18. Table 18
[0527] The 25% vamorolone/HPMCAS-H and 25% vamorolone/EUDRAGIT® L100 SDDs showed the best performance enhancement, with approximately a 4.8-fold and 4.6- fold increase in FaSSIF AUC, respectively, relative to micronized vamorolone. The 50% vamorolone/CAP SDD showed an approximate 1.9-fold increase in FaSSIF AUC. The 25% vamorolone/PAA SDD showed no significant performance enhancement relative to neat vamorolone. Both the 25% vamorolone/PAA and 50% vamorolone/CAP SDDs showed some recrystallization occur in the gastric phase, likely leading to lower sustained intestinal concentrations compared to the 25% vamorolone/HPMCAS-H and 25% Vamorolone/EUDRAGIT® L100 SDDs.
Example 4b: Additional Vamorolone Amorphous Solid Dispersions Prepared by Spray Drying [0528] Vamorolone amorphous solid dispersions were prepared by spray drying. The solid dispersions and spray drying conditions that were used to prepare the dispersions are shown in Tables 19 and 20. All spray drying was performed using a Büchi B-290 with B- 295 Condenser (recycle mode) spray dryer with a two-fluid nozzle with 1.5 mm air cap and 0.7 mm liquid tip and high efficiency cyclone. The batch size was 20 g (solids) for each formulation. Table 19
Table 20
XRPD [0529] The formulations were characterized by XRPD using XRPD Method 3. The solid dispersions described in Tables 19 and 20 above were all amorphous. DSC [0530] The formulations were also characterized by DSC using DSC Method 3. The results are shown in Table 21. Table 21
[0531] The solid dispersions each had a single glass transition indicating a homogenous amorphous dispersion.
Scanning Electron Microscopy (SEM) [0532] The solid dispersions were also characterized by SEM using a Phenom XL2 instrument. The formulations exhibited a shriveled sphere particle morphology. No evidence of crystalline vamorolone was observed. Non-Sink Dissolution in Biorelevant Media [0533] The dissolution behavior of the solid dispersions was measured by non-sink dissolution using Non-Sink Dissolution Test Method 2. [0534] The results are shown in Table 22. All formulations provided an increase in FaSSIF AUC relative to both crystalline vamorolone and an oral suspension of vamorolone. Table 22
Example 5: Bead or Powder Substrates Coated with Vamorolone by Fluid Bed Drug Layering [0535] Fluid bed drug layering is the principle of applying drug substance onto a substrate, usually in the form of multiple unit pellet system (MUPS) or substrate powder, in a fluid bed by bottom spray (Wurster process), top spray, or tangential spray. Crystalline vamorolone and a polymer are co-dissolved in one or more solvents. The solution is sprayed onto substrate pellets or powders and simultaneously dried in a fluid bed (Wurster spray, top spray, or tangential spray setup). The one or more solvents are
removed during the process by air or nitrogen. The output material is a substrate comprising an amorphous drug layer. Multiple Unit Pellet System (MUPS) [0536] For MUPS, the substrates on which an amorphous drug layer is sprayed are, e.g., sugar spheres, microcrystalline cellulose (MCC) spheres, or silica spheres. The amorphous drug layered substrates are coated with a layer of seal coating using the same or a different polymer as used for the vamorolone layer, to ensure the chemical stability of vamorolone throughout the shelf life of the final drug product. The output pellets are used as is (encapsulated) or are processed further, as described in Examples 6 and 7. Impregnation: Drug Layering/Granulating with Powder Substrate [0537] An amorphous drug layer is sprayed on powder substrates, e.g., dibasic calcium phosphate anhydrous (DCPA), magnesium alumino-metasilicate (NEUSILIN®), or microcrystalline cellulose. Seal coating is applied with the same polymer for the vamorolone layer, to ensure the chemical stability of vamorolone throughout the shelf life of the final drug product. The amorphous vamorolone impregntated powder is used as is (encapsulated) or can be processed further, as described in Examples 6 and 7. [0538] Exemplary bead or powder substrates coated with vamorolone by fluid bed drug layering are shown in Table 23. Table 23
Example 6: Powder-in-Capsule or Tablet Formulations Comprising Amorphous Solid Dispersions Comprising Vamorolone [0539] Amorphous solid dispersions comprising vamorolone, e.g., those described in Examples 1-4, or bead or powder substrates coated with vamorolone, e.g., those described in Example 5, are encapsulated or compressed into tablets or minitablets. The tablets are packaged as-is or are film-coated. Exemplary powder-in-capsule or tablet formulations are shown in Tables 24 and 25.
Table 24
Table 25
Example 6a: Capsule Formulations Comprising Amorphous Solid Dispersions Comprising Vamorolone [0540] Capsules comprising the HMEs prepared as described in Example 1b were prepared. All capsules were size 0 HPMC capsules. Capsules were prepared comprising either HME granules only or a formulation comprising HME granules and additional components. [0541] Capsules containing HME granules only were filled at 300 mg/unit for 10% drug load, 150 mg/unit for 20% drug load, or 100 mg/unit for 30% drug load. [0542] The formulations comprising HME granules and additional components contained 75 wt% HME granules, 19.5 wt% microcrystalline cellulose (PH102), 5 wt% croscarmellose sodium (AC-DI-SOL®) and 0.5 wt% magnesium stearate. Capsules containing the formulation were filled at 400 mg/unit for 10% drug load, 200 mg/unit for 20% drug load, or 133 mg/unit for 30% drug load. [0543] The dissolution behavior of the capsules was analyzed using Non-Sink Dissolution Test Method 1. The results are shown in FIGS.16 and 17 (capsules containing HME granules only) and FIGS.18 and 19 (capsules containing formulation).
Example 6b: Tablet Formulations Comprising Amorphous Solid Dispersions Comprising Vamorolone [0544] The amorphous solid dispersions comprising vamorolone prepared in Example 1b were compressed into tablets. Tablets were prepared from milled hot melt extrudate granules comprising 20-40% vamorolone and PVP K30, as shown in Table 26. The tablets were compressed with 0.3000" * 0.5700" (7.62 mm * 14.48 mm) mod oval tooling. Table 26
[0545] The drug dissolution behavior of the tablets was studied using Non-Sink Dissolution Test Method 1. The results are shown in FIG.20. [0546] The impact of tablet hardness and tablet weight on drug dissolution was also studied, as shown in FIGS.21 and 22, respectively. [0547] Additional tablets were also prepared using KOLLIDON® VA64 in place of PVP K-30. FIG.23 compares the dissolution behavior of tablets prepared from PVP K-30 and KOLLIDON® VA64. Example 6c: Additional Tablet Formulations Comprising Amorphous Solid Dispersions Comprising Vamorolone [0548] The amorphous solid dispersions comprising vamorolone prepared in Example 4a were compressed into tablets. Tablets were prepared as described in Tables 27 and 28.
Table 27
Table 28
[0549] The dissolution behavior of the tablets was studied using Non-Sink Dissolution Test Method 1. The results are shown in FIG.24. Example 6d: Additional Tablet Formulations Comprising Amorphous Solid Dispersions Comprising Vamorolone [0550] The amorphous solid dispersions comprising vamorolone prepared in Example 4b were compressed into tablets. [0551] Intragranular components were mixed in a turbula blender for about 5 minutes at about 22 rpm, sieved and de-lumped using a 20 mesh sieve, and further mixed in a turbula blender for about 5 minutes at about 22 rpm. The mixture was slugged using a Natoli single station press with 2.225 mm FF tooling and a target S.F. of 0.60-0.70, then milled using a Gerteis hand mill and 1mm screen to generate granules. The granules were mixed with the extragranular components in a turbula blender for about 10 minutes at about 22 rpm. Tablets were prepared using a Styl'One Nano using a compressing pressure range of 50-200 MPa and the following tooling: 6.363 mm x 13.68 mm Mod Capsule; 6.350 mm SRC; 7.142 mm SRC; or 8.999 mm x 17.90 mm Mod Capsule. The resulting tablet
formulations are listed in Table 29. The total masses of tablet formulations F134-F137 were each 375 mg (containing 30 mg vamorolone); and the total masses of tablet formulations F138-F140 were each either 166 mg (containing 30 mg of vamorolone) or 833 mg (containing 150 mg vamorolone). Table 29
*Both 166 mg (containing 30 mg of vamorolone) and 833 mg (containing 150 mg vamorolone) tablets were produced. **0.2500" SRC was also used for compression profile. [0552] The compressibility, compactibility, tabletability, and disintegration time of tablets prepared using different compression pressures were measured using the procedures for measuring tablet characteristics described in the General Methods section above. The results are shown in FIGS.25-36 and Table 30. Table 30
[0553] Vamorolone tablets comprising formulations 134-140 were manufactured in bulk as described in Table 31. Table 31
[0554] The drug dissolution behavior of the tablets was studied using Non-Sink Dissolution Test Method 2. The results are shown in Table 32. Table 32
[0555] The 20:80 Vamorolone:HPMCAS-M SDI 30 mg tablet reached the highest concentration, but showed a steady decrease after gastric transfer. The 30 mg EUDRAGIT® SDI tablet also demonstrated a large decrease, and maintained the lowest API conc. The other SDI tablets demonstrated good sustainment. Overall, the tablets exhibited 3 to 5 times higher FaSSIF AUC relative to crystalline vamorolone. Example 7: Powder-For-Suspension Formulations Comprisng Amorphous Solid Dispersions Comprising Vamorolone [0556] Amorphous solid dispersions comprising vamorolone, e.g., those described in Examples 1-4, or bead or powder substrates coated with vamorolone, e.g., those described in Example 5, are blended with pharmaceutically acceptable excipients to produce a powder that is later mixed with a liquid to form a suspension for oral administration. Exemplary powder-for-suspension formulations are shown in Table 33.
Table 33
Example 8: Tablet or Capsule Solid Oral Dosage Forms Comprising Solid Amorphous Dispersions Comprising Vamorolone [0557] Solid amorphous dispersions comprising vamorolone having Formulae IF42 through IF47, as shown in Table 34, are prepared and are incorporated into a tablet or capsule, as described below. Table 34
120% solids content solution is prepared. Solvent is evaporated during the process and is therefore not included in the formula. Batch size is 75g. Procedure for Polymer-Based Solid Dispersions (IF41, IF42, IF46, IF47) [0558] Ingredients are weighed as per the pharmacy weighing sheet of the batch record. The quantity of vamorolone is adjusted based on assay and water content. [0559] Vamorolone and polymer are dissolved in a suitable solvent (e.g., methanol/ethanol) to form a 20 wt% solids content solution. [0560] The solution is vacuum dried using a vacuum oven and vapor trap to afford the polymer-based solid dispersion. Procedure for Carrier-Based Solid Dispersions (IF43, IF44) [0561] Vamorolone and polymer are dissolved in a suitable solvent (e.g., methanol) to form a 20 wt% solids content solution. [0562] Silica is dispersed in the vamorolone solution. The solution is stirred until a homogeneous mixture is obtained. [0563] The mixture is vacuum dried using a vacuum oven and vapor trap to afford the carrier-based solid dispersion. Procedure for Preparing Tablets or Capsules [0564] The polymer-based or carrier-based solid dispersion (e.g., IF43 through IF47) is blended in a polyethylene (PE) bag with one or more pharmaceutically acceptable excipients, e.g., one or more diluents, one or more binders, one or more disintegrants, one or more lubricants, or a combination thereof, to prepare a blend. [0565] One to three unit-dose samples from different locations of the PE bag is optionally collected using an appropriately sized sample thief.
[0566] Tablets are prepared by compressing the blend, e.g., to the specifications shown in Table 35. Table 35
[0567] Capsules are prepared by filling size 3 capsules to 150 mg fill weight or size 00 capsules to 500 mg fill weight. The capsules are prepared to have the specifications shown in Table 36. Table 36
Example 9: Vamorolone Oral Dosage Tablets Prepared using High Shear Granulation [0568] Vamorolone oral dosage tablets are prepared using the procedure described below and shown in FIG.1. [0569] 1. Weigh the excipients. [0570] 2. Add vamorolone to a solvent, e.g., benzyl alcohol, tetrahydrofuran, m- cresol, or any combination of the foregoing, in a separate container and mix them to prepare a solution. [0571] 3. Add cellulose microcrystalline (diluent-1), binder/disintegrant/filler/diluent as listed in Tables 37-41 below (e.g., lactose for F23, lactose monohydrate for F24, starch for F25, etc.), and a portion of mannitol (diluent-2) to a granulating bowl and mix. [0572] 4. Slowly add vamorolone solution to the material in the granulating bowl during granulation to prepare granules. [0573] 5. Perform wet milling of prepared wet granules. [0574] 6. Dry the wet granules appropriately. [0575] 7. Perform the milling of the dried granules.
[0576] 8. Perform milling of the remaining portion of mannitol (diluent-2) from the same mil. [0577] 9. Perform sieving of the dried granules. [0578] 10. Perform pre-lubrication blending of above milled material by adding croscarmellose sodium (disintegrant) and colloidal silicon dioxide (glidant). [0579] 11. Sieve the magnesium stearate (lubricant) and then add the above blended material. [0580] 12. Perform lubrication blending. [0581] 13. Discharge the final blend from the blender. [0582] 14. Perform compression of the above prepared blend to produce tablets. [0583] Formulations F23-F53, shown in Tables 37-41 below, are prepared using this procedure. Table 37
Table 38
Table 39
Table 40
Table 41
Example 10: Vamorolone Oral Dosage Tablets Prepared using Top Spray Granulation [0584] Vamorolone oral dosage tablets are prepared using the procedure described below and shown in FIG.2. [0585] 1. Weigh the excipients. [0586] 2. Add vamorolone and binder/disintegrant/filler/diluent as listed in Tables 42-46 below (e.g., lactose for F54, lactose monohydrate for F55, starch for F56, etc.) to a solvent, e.g., benzyl alcohol, tetrahydrofuran, m-cresol, or any combination of the foregoing, in a separate container and mix to prepare a solution. [0587] 3. Add mannitol (diluent-1) in the fluid bed. [0588] 4. Spray the above-prepared solution onto the mannitol (diluent-1). [0589] 5. Perform drying of the granules. [0590] 6. Perform milling of the dried granules. [0591] 7. Perform milling of the microcrystalline cellulose using the same mil. [0592] 8. Perform sieving of the dried granules. [0593] 9. Perform pre-lubrication blending of above milled material by adding croscarmellose sodium (disintegrant) and colloidal silicon dioxide (glidant). [0594] 10. Sieve the magnesium stearate (lubricant) and then add in the above blended material. [0595] 11. Perform lubrication blending. [0596] 12. Discharge the final blend from the blender. [0597] 13. Perform compression of the above prepared blend to produce tablets.
[0598] Formulations F54-F84, shown in Tables 42-46 below, are prepared using this procedure. Table 42
Table 43
Table 44
Table 45
Table 46
Example 10a: Vamorolone Oral Dosage Tablets and Capsules Prepared using Top Spray Granulation [0599] Vamorolone oral dosage tablets and capsules were prepared using top spray granulation. Step 1: Solution Preparation [0600] Solvent was weighed in a container. The appropriate polymer was slowly dissolved in the solvent by air mixer until fully dissolved. Vamorolone was then added to the polymer solution and mixed until a homogenous suspension/solution was obtained. Step 2: Fluid Bed Granulation (Top Spray) [0601] Fluid bed granulation was performed using the process parameters shown in Table 47. Table 47
*Adjusted to maintain product temperature [0602] A VECTOR® fluid bed was prepared as described in Table 48. Table 48
[0603] A peristaltic pump was set to a delivery rate of about 5-30 g/min. The fluid bed chamber was pre-heated for about 15 minutes. [0604] Mannitol 200 SD was weighed, passed through a sieve (#20 Mesh), loaded onto the fluid bed, and pre-heated in the fluid bed until reaching a temperature of about 40 °C. The vamorolone/polymer solution was then sprayed onto the mannitol using the top-spray nozzle per the parameters listed in Table 47. When spraying was completed, the granules were dried and cooled per the parameters listed in Table 47. Step 3: Comiling or Screening [0605] The granules obtained in step 2 were either comiled per the parameters listed in Table 49 or were passed through a hand screen (Mesh #18). Table 49
Step 4: Blending and Lubrication [0606] Approximately 200 g of the granules obtained from Step 3 were transferred to a suitable size turbula blender. The appropriate quantities of mannitol 200 SD (extragranular), croscarmellose sodium, and silicon dioxide were added to a polybag, manually mixed, passed through a hand screen (Mesh #20), and added to the turbula blender. The resulting mixture was blended for about 10 minutes. The appropriate quantity of magnesium stearate was passed through a hand screen (Mesh #20) and added to the existing mixture in the turbula blender, and the resulting mixture was blended for about 5 minutes to produce the final formulations, which are listed in Table 50 below. Table 50
*Evaporated during process; Q.S. = Quantity Sufficient [0607] The formulations each had a final weight of 400 mg. Formulations F141-F149 were compressed into tablets having low hardness (6-7 kp), target hardness (11 kp), or high hardness (17-18 kp); or were encapsulated in size 00 capsules.
X-Ray Powder Diffraction (XRPD) [0608] The vamorolone tablets and capsules were analyzed by XRPD using XRPD Method 3. The XRPD spectra largely matched the XRPD spectrum for mannitol 200 SD alone, but also included crystalline vamorolone peaks at about 8, 12, and 16 degrees 2Θ. Non-Sink Dissolution in Biorelevant Media [0609] The dissolution behavior of the vamorolone tablets and capsules was measured by non-sink dissolution using Non-Sink Dissolution Test Method 2. The results are shown in Table 51. Table 51
Example 11: Vamorolone Oral Dosage Tablets Prepared using High Shear Granulation and a Lipid Binder [0610] Vamorolone oral dosage tablets are prepared using the procedure described below and shown in FIG.3. [0611] 1. Weigh the excipients. [0612] 2. Add vamorolone to a solvent, e.g., benzyl alcohol, tetrahydrofuran, m- cresol, or any combination of the foregoing, and mix to prepare a solution. [0613] 3. If using, melt the glyceryl behenate (binder) if it is waxy/lipidic. [0614] 4. Add cellulose microcrystalline (diluent-1), binder as listed in Table 52 below (e.g., acacia for F85, agar for F86, etc.), and a portion of mannitol (diluent-2) in a granulating bowl and mix. [0615] 5. Slowly add above prepared vamorolone solution to the material in the granulating bowl during granulation to prepare granules. [0616] 6. Perform wet milling of prepared wet granules. [0617] 7. Dry the wet granules appropriately. [0618] 8. Perform milling of the dried granules. [0619] 9. Perform milling of a portion of Mannitol (diluent-2) from the same mil. [0620] 10. Perform sieving of the dried granules. [0621] 11. Perform pre-lubrication blending of above milled material by adding croscarmellose sodium (disintegrant) and colloidal silicon dioxide (glidant). [0622] 12. Sieve the magnesium stearate (lubricant), then add the above blended material. [0623] 13. Perform lubrication blending. [0624] 14. Discharge the final blend from the blender. [0625] 15. Perform compression of the above prepared blend to produce tablets.
[0626] Formulations F85-F91, shown in Table 52 below, are prepared using this procedure. Table 52
Example 12: Vamorolone Oral Dosage Tablets Prepared using High Shear Granulation and a Lipid Carrier [0627] Vamorolone oral dosage tablets are prepared using the procedure described below and shown in FIG.4. [0628] 1. Weigh the excipients. [0629] 2. Add vamorolone to the lipid carrier and mix to prepare a dispersion. [0630] 3. Add cellulose microcrystalline (diluent-1), and a portion of mannitol (diluent-2) to the granulating bowl and mix. [0631] 4. Slowly add above prepared vamorolone dispersion to the material in the granulating bowl during granulation to prepare granules. [0632] 5. Perform wet milling of prepared wet granules. [0633] 6. Dry the wet granules appropriately. [0634] 7. Perform the milling of the dried granules. [0635] 8. Perform milling of the remaining part of mannitol (diluent-2) from the same mil. [0636] 9. Perform sieving of the dried granules. [0637] 10. Perform pre-lubrication blending of above milled material by adding croscarmellose sodium (disintegrant) and colloidal silicon dioxide (glidant). [0638] 11. Sieve the magnesium stearate (lubricant) and then add in the above blended material. [0639] 13. Perform lubrication blending. [0640] 14. Discharge the final blend from the blender. [0641] 15. Perform compression of the above prepared blend to produce tablets. [0642] Formulations F92-F94, shown in Table 53 below, are prepared using this procedure. Table 53
Example 13: Vamorolone Oral Dosage Tablets Prepared using High Shear Granulation and Cyclodextrin Complexation [0643] Vamorolone oral dosage tablets are prepared using the procedure described below and shown in FIG.5. [0644] 1. Weigh the excipients. [0645] 2. Add vamorolone and cyclodextrin (solubilizing agent) to a solvent, e.g., benzyl alcohol, tetrahydrofuran, m-cresol, or any combination of the foregoing, and mix to prepare a solution. [0646] 3. Add cellulose microcrystalline (diluent-1), hydroxypropyl methylcellulose (hypromellose) (binder), and a portion of mannitol (diluent-2) in the granulating bowl, and mix. [0647] 4. Slowly add prepared vamorolone solution to the material in the granulating bowl during granulation to prepare granules. [0648] 5. Perform wet milling of prepared wet granules. [0649] 6. Dry the wet granules appropriately. [0650] 7. Perform milling of the dried granules. [0651] 8. Perform milling of the remaining portion of mannitol (diluent-2) from the same mil. [0652] 9. Perform sieving of the dried granules. [0653] 10. Perform pre-lubrication blending of above milled material by adding croscarmellose sodium (disintegrant) and colloidal silicon dioxide (glidant). [0654] 11. Sieve the magnesium stearate (lubricant) and then add the above blended material. [0655] 12. Perform lubrication blending. [0656] 13. Discharge the final blend from the blender. [0657] 14. Perform compression of the above prepared blend to produce tablets.
[0658] Formulations F95-F100, shown in Table 54 below, are prepared using this procedure. Table 54
Example 13a: Vamorolone Oral Dosage Tablets and Capsules Prepared using High Shear Granulation and a Lipid Carrier or Cyclodextrin Complexation [0659] Vamorolone oral dosage tablets and capsules were prepared using high shear granulation. Preliminary Cyclodextrin Solubility Tests [0660] Prior to preparing the formulations, the aqueous solubility of vamorolone in the presence of different solubilizing agents was determined. [0661] 170 mg of CAVAMAX® W7 (beta-cyclodextrin) was dissolved in 10 mL of purified water to provide a solution.50 mg of micronized vamorolone was added to the solution and stirred continuously overnight, which resulted in a turbid suspension.
Addition of 10 mL of ethyl alcohol did not appear to improve the solubility of the vamorolone. [0662] 4100 mg of KLEPTOSE® HPB (hydroxypropyl beta-cyclodextrin) oral grade was dissolved in 5 mL purified water to provide a 820 mg/mL solution. Vamorolone was added to the solution gradually until the solution became turbid. Approximately 365 mg of vamorolone was added without any change in the turbidity of the solution. Based on these observations, the solubility of vamorolone in a 820 mg/mL KLEPTOSE® HPB aqueous solution was about 73 mg/mL. Preliminary Lipid Solubility Tests [0663] The solubility of vamorolone in aqueous solvents comprising various lipid excipients was determined by adding vamorolone to 10 mL of the excipient at from about 37 °C to about 57 °C until the solution became turbid. The results are shown in Table 55. Table 55
Preparation of Vamorolone Cyclodextrin Formulation [0664] A formulation comprising vamorolone and KLEPTOSE® HPB (hydroxypropyl beta-cyclodextrin) oral grade was prepared and compressed into tablets or capsules comprising 30 mg vamorolone. The components of the formulation (F173) are shown in Table 56.
Table 56
Step 1: Granulating Solution Preparation [0665] 50 g of purified water was weighed in a glass beaker. KLEPTOSE® HPB oral grade was added slowly to the purified water with continuous stirring until the KLEPTOSE® HPB was fully dispersed. Vamorolone was then slowly added to the solution with continuous stirring until fully dispersed. The solution was sonicated for 15 minutes. Step 2: Wet Granulation [0666] Microcrystalline cellulose and mannitol were weighed into separate polybags, then loaded into a KG-5 granulator and mixed for 5 minutes at an impeller set speed of 200 rpm with the chopper off. Granulation was performed by gradually spraying the granulating solution onto the Microcrystalline cellulose/mannitol dry blend while the impeller and chopper were running. Additional purified water was used as needed to achieve desired granules. Step 3: Wet Milling [0667] The resulting wet granules were milled using a Quadro Comil U5 ID with a 7L312Q screen, a 7L1601 (Round) impeller, and a target speed of 1500 RPM.
Step 4: Fluid Bed Drying of Wet Granules [0668] The Vector fluid bed was pre-heated to about 55 °C with an air volume of about 60 CFM. The granules from step 3 were dried in the Vector product bowl at 55 °C for about 35 minutes. Step 5: Comiling or Screening [0669] The granules obtained in step 3 were passed through a #18 mesh hand screen. Step 6: Blending, Lubrication, and Tablet/Capsule Formation [0670] The granules from step 5 were transferred to a turbula blender. The appropriate quantities of croscarmellose sodium (extragranular) and silicon dioxide colloidal (extragranular) were added to a polybag and mixed manually, then passed through a #20 mesh hand screen. The screened material was added to the blender and mixed for about 10 minutes. The resulting material was screened through a #20 mesh hand screen and returned to the blender. Magnesium stearate was screened through a #20 mesh hand screen and added to the blender, and the mixture was blended for 5 minutes. The resulting material was compressed into tablets having hardnesses of about 7 kp (low hardness), about 11 kp (target hardness), or about 17 kp (high hardness), or filled into 00 capsules. The final tablets and capsules contained 30 mg vamorolone. Preparation of Vamorolone Lipid Formulation [0671] A formulation comprising vamorolone and was prepared and compressed into tablets or capsules comprising 30 mg vamorolone. The components of the formulation (F174) are shown in Table 57. Table 57
Step 1: Pre-Mixing in High Shear Granulator [0672] The intragranular excipients listed in Table 57 were loaded into a high shear granulator and dry mixed for about 5 minutes. Step 2: Spraying Lipid in High Shear Granulator [0673] LABRASOL® solution was sprayed onto the powder blend prepared in step 1 while the impeller and chopper were running. The spray rate was controlled as needed to ensure even distribution and prevent overwetting. Step 3: Wet Milling of Granules [0674] The wet granules obtained from step 2 were transferred to a Quadro Comil and milled to achieve a uniform granule size. Step 4: Extragranulation Mixing [0675] The milled granules obtained in step 3 were transferred to a blender and mixed with the extragranular components listed in Table 57. Step 5: Final Processing – Capsule Filling or Direct Compression [0676] The mixture obtained in step 4 was either compressed into tablets having hardness of 4 kp (low hardness), 6 kp (target hardness), or 8 kp (high hardness) or filled into capsules. The final tablets and capsules contained 30 mg of vamorolone. Non-Sink Dissolution Testing [0677] Non-sink dissolution studies were conducted using Non-Sink Dissolution Test Method 2. The results are shown in Table 58. The beta-cyclodextrin based tablets (F173)
exhibited a 1.7-fold increase in FaSSIF AUC relative to an oral suspension of vamorolone. Table 58
Example 14: Vamorolone Oral Dosage Capsules Prepared using Drug Layering [0678] Vamorolone oral dosage tablets are prepared using the procedure described below and shown in FIG.6. [0679] 1. Weigh the excipients. [0680] 2. Add vamorolone, povidone, cellulose acetate, poly(ethylene glycol), ethyl cellulose, or polyvinyl acetate; and triethyl citrate (plasticizer) to a solvent, e.g., benzyl alcohol, tetrahydrofuran, m-cresol, or any combination of the foregoing, and mix to prepare a solution. [0681] 3. Add sugar spheres (carrier) to the fluid bed. [0682] 4. Spray above prepared solution onto the sugar spheres (carrier). [0683] 5. Perform drying of drug layered sugar spheres. [0684] 6. Perform sieving of drug layered sugar spheres.
[0685] 7. Add OPADRY® Clear (film coating agent), hydroxypropyl methylcellulose (HPMC) (binder) in purified water (solvent) in a separate container and mix to prepare a solution for seal coating. [0686] 8. Add drug layered sugar spheres to the fluid bed. [0687] 9. Spray the above prepared seal coating solution onto the drug layered sugar spheres. [0688] 10. Perform drying of seal coated sugar spheres. [0689] 11. Perform sieving of seal coated sugar spheres. [0690] 12. Perform pre-lubrication blending of above sieved seal coated sugar spheres by adding croscarmellose sodium (disintegrant) and colloidal silicon dioxide (glidant). [0691] 13. Sieve the magnesium stearate (lubricant) and then add in the above blended material. [0692] 14. Perform lubrication blending. [0693] 15. Discharge the final blend from the blender. [0694] 16. Perform encapsulation of the above prepared blend to produce capsules. [0695] Formulations F101-F105, shown in Table 59 below, are prepared using this procedure. Table 59
Example 15: Vamorolone Oral Dosage Forms Prepared by Direct Blending [0696] Formulations F106-F123 (see Tables 60-63 below) are prepared using the procedure described below and in FIG.7. [0697] 1. Weigh all the ingredients as per the pharmacy weighing sheet of the batch record. Adjust the vamorolone quantity based on assay and water content. [0698] 2. Pre-blend: Add diluent 1 to the V-blender and mix for 2 minutes at 25±1 RPM. Add crystalline vamorolone, followed by binder, disintegrant, and diluent 2, to the V-blender and mix for 10 minutes at 25±1RPM. Discharge the blend into a PE bag. [0699] 3. Milling: Pass the pre-blend through a Quadro Comil equipped with 20 mesh screen at low speed. [0700] 4. Blending: After milling, transfer the pre-blend to the 2V blender. Mix for 12 minutes at 25±1 RPM. [0701] 5. Lubrication: Screen the lubricant through a 30-mesh hand screen. Add the screened material to the V-blender and mix for 3 minutes at 25±1 RPM. [0702] 6. Sampling from V blender (optional): Collect one to three unit-dose samples from 3-5 different locations of the V blender using an appropriately sized sample thief.
11 52 . 5 7 7 . 0 0 . 0 0 0 0 0 . F 0 w / 0 0 . 3 1 . 8 3 . 0 0 0 0 0 5 0 . 0 4 5 1 0 1 . 5 . 2 0 1 w %0 2 8 5 9 1 . 1 . 1 . 0 0 1
8 3 . 3 1 . 0 . 0 5 0 . 0 a l w / 0 0 . 0 0 0 0 0 0 0 0 . a l 8 0 . 5 . 0 0 u w0 . . 0 . 0 . 0 . 0 u 4 6 1 1 1 m r o % 2 7 5 9 1 1 1 2 0 1 m r f o f 52 . 5 0 0 0 h c b 1 7 a 0 0 0 0 0 h c 0 . 1 3 0 . 0 3 0 0 5 . 5 0 . . 0 0 a 1 0 5 e t / 0 . n 0 0 . 5 0 . 0 0 . 0 0 . 0 . . 0 a e i g 0 3 3 1 5 4 5 5 0 1 0 5 n d 3 1 m i d 5 0 0 e s 1 F 0 e s 2. 5 0 7 2 . 6 0 . 0 0 0 1 . 0 1 0 . . 2 0 u 0 s w / 0 . 0 0 . 0 0 1 t n w0 7 . 0 0 . 0 0 . 0 0 0 . 0 u s e 9 1 1 . 2 0 t i % 6 2 1 n e p i i c p i 9 1 . 7 x b c x 7 0 . 0 5 8 9 2 . 0 1 5 . 5 1 7 0 . . 0 0 5 e a t 1 ci / 0 0 . 9 6 . 7 5 . 0 5 f . 0 5 5 7 0 . 0 e i g 0 2 7 1 . 7 . 0 5 ci c 2 m 3 8 2 1 f i e 1 c p 1 e 31 . 8 8 3 . 0 5 9 1 . 1 0 . 1 5 . 0 0 . 0 s F 0 r w / 0 0 . 3 1 . 8 3 . 0 0 0 0 0 5 0 . p s r 1 o f w 3 %0 2 5 5 8 1 . 1 . 5 . 0 0 0 1 o f a 6 t e 1 3 6 a 6 e 1 a t 2 a n t r n a a r t l n l b a e l l a e i n o l a 1 a 2 t a r n a at l n l b a e n e e d g e a c i a r t T b a r e o r t n t e n e e r d g e a c i a t T uli uli n i t B n i b o T o t T t a o mul i ul i n i t B n i r b o T o t D D s i u D L r e f M e a V D D s i u D L r e f e 2 3 3 4 5 a R # 1 2 3 3 4 5 a R
6 n 5 . 9 2 1 . 0 0 . 0 5 5 0 . a u i c i s e c A l c y r s u i m s c u e A u i c s e c A l c y r 7 4 2 5 1 . 7 7 . 0 0 5 r 1 b n u g i L a r e e c y Mt S l i d n g i G o S a r n e g i M t S a r e e c y M t S l G 83 3 1 0 0 0 0 0 .
2 . 1 7 0 . 0 . 0 0 0 . . 0 a e o o o 1 3 3 0 5 . 5 0 1 0 5 n h i p h p h p d 5 e 2 m m s t e u i e t a r e u i e t a m r e u i 2 . 5 0 0 7 0 0 0 0 . u n e s h c l u o t c r a c d y s o t h c r c l a d y s o t h c r c l a 2 . 6 . 0 0 1 . 1 0 . 2 0 0 s 1 t n li c a h c a c h c a c Da L t i i a t i i a t i ei S D D L S D D L S D pi 8 8 . 3 0 6 . 0 0 . 0 5 7 3 2 5 1 . 0 7 0 0 c . . 3 0 x 5 e e 1 ci s e e e e e e e e f o i l s c u l o l l s ul o l l s ul o l l s ul o l l s ul o l l u l ni l ll ni a l t l ni a l t l a t 5 2 . 5 0 e p eCeC eC eC eC eC s y s y s y 7 7 . 4 5 0 . 0 0 0 . s 1 0 0 1 . 5 0 . 2 0 0 1 r o e f ni e ll ni e ll ni e ll ni e ll ni e r ll ni c r ll o r c r o r c o r 3 a t a t a t a t a t a t c i c M i c i a 1 a t 6 1 e 3 t s n y r s c y r s c y r s c y r s c y r s c y r c d e e s M o d e e s M o d e t 2 a n t e n r n e a a r t n l l b 6 e e o r o r o r o r o r o r ifi c l u l ifi c l u l ifi u d g a c i a t a l u T b li c i c i c i c i c i c i il i l e il i l e c il i l e i uli n i e t n i r b o T o a T D M M M M M M S C S C S D D B s i u t D L r e f e # 6 0 7 8 9 0 1 2 3 4 1 0 1 0 1 0 1 1 1 1 1 2 3 3 4 5 a R F F F F 1 F 1 F 1 F 1 F 1 F 1 F
o o c o o o o S y S c y S c y e l G e l G e l s o l l h e s e s G e e c r n o o m d l h i l e c r n o o d l h i l e c r n o d i r a t v m r a t S v m r a t v a S o a o a S o c s s m u P i s c s s s m u P i s c s m u P i s o r d o r o r d s o r s o d s o C o S C Co S C r C o S r C 0 4 4 3 - 6 K a 6 a 0 3 - w o b w o b P C V M V CV K L u S / C L u S / P P P M H V P P P P C H V P V P P WM H MP C H P W H M et a e t e t h a a p h p h s o s p s h o o p h p h p e m s u o i e t a me me t h r e u i t a r e u i t a r c c r c l a d a a c y s o t h c r c l a d y s o t h c c l a d y L t S i h Di c a c D a L t S i h c r a c h Di D a L t S i Di D eni e e ll ni a l ni t l s a l t l r s a t y c y r s y r o r c ci o r c c o r c M i d e M i d e M d e l l l l l l e i s fi o c l e i s o l e i s o o t i o t i o t i o t i o t i o t i il u i l l fi c u l l fi c l u l l n n n n n n n n n n n n S e i Cl i S e i Cl i S e Ca Ma M a M a M a M a M 51 6 1 7 8 9 0 1 2 3 1 1 1 1 2 2 2 2 F 1 F 1 F 1 F 1 F 1 F 1 F 1 F 1 F
[0703] Tablets are prepared by compressing one of formulations F106-F123 according to specification in Table 64. Table 64
[0704] Capsules having the specifications in Table 65 are prepared by filling one of formulations F106-F123 into hard gelatin/HPMC capsules (using size 3 capsules for 150 mg fill weight and size 00 capsules for 500 mg fill weight). Table 65
Example 15a: Vamorolone Oral Dosage Forms Prepared by Direct Blending [0705] Formulations F150-F158, F164-172, and F175 described in Tables 66-69 were prepared by direct blending. [0706] Diluent 1 was added to a polyethylene (PE) bag and mixed. Then crystalline vamorolone, binder, disintegrant, and diluent 2 were added to the PE bag and mixed. The mixture was screened through a 20 mesh screen and further mixed. Lubricant was separately screened through a 30 mesh screen, then added to the PE bag and mixed. The resulting mixture was compressed into a tablet using a Carver press at the hardness specified below.
4 5 m % 1 F w / w0 7 9 b 1 1 0 a t / 0 9 . 2 7 . 5 6 . 9 . 1 . 1 . 7 %2 5 1 2 0 1 5 g 0 3 1 7 8 2 4 7 1 5 6 3 1 8 1 m F
% 4 2 m r o F m r b f w / w0 2 4 . 8 1 . 5 5 5 . 0 0 o f at / 0 6 9 4 1 2 0 1 0 h c % h c 1 g 0 . 0 . 6 5 5 5 . 2 0 a e a e 5 m 3 9 9 5 n b a t 5 . 5 . 5 5 0 n 1 i / F d g 0 3 5 8 . 1 . 1 3 5 1 i w/ 1 4 e s 7 5 8 2 d e 1 m s w0 % 6 . 8 . 1 9 1 1 1 5 . 0 0 0 1 u st F u s n w e / i w0 2 7 5 9 1 1 1 2 0 0 t 1 n e b p a i % i t / g 0 3 2 . 7 1 . 7 5 . 1 5 . 1 8 . 0 c p i 0 5 x e b c a t 9 6 5 5 5 0 x e 0 8 2 1 5 m c / 0 3 . 0 . 5 . 1 i f 4 . . 5 c F i 6 g m 7 3 7 1 1 i f i w / 2 w0 2 1 . 8 c 3. 1 1 5 . 0 e 5 0 p 1 c s F w / e 2 . 8 . 0 p s % 8 5 9 1 0 1 r o f w0 % 2 7 4 3 2 3 5 1 0 1 r o f l a e i n a a r o l o 1 a t 2 t t a r n e a a 9 r t 6 9 g n a l a e l 7 6 n o i t l a e n a o a 1 a 2 t a r n a at 6 n l e l # e t a r o n e n Mmu a l e d i uli n i e t c B n i i r t b o b T a e l T b a i r l a u l # e t o r t o n t e n e e r d g e a t c i a b r t o a T V D D s i u D L o tr T m r a Mmuli uli n i B n i e o a D D s b i u T o t # 1 2 3 3 4 5 f F V D L r e e f e a R # 1 2 3 3 4 5 a R
at / 0 7 . 0 7 g 0 . 9 . 3 1 . 3 4 6 6 1 5 2 . 4 7 5 2 m 2 8 4 8 7 1 F w / w5 3 9 . 0 6 . 8 0 1 5 5 . 0 0 0 % 3 1 1 b a t / 0 1 g 0 7 3 . 0 5 8 6 7 . 1 5 6 8 . 8 1 . 1 7 . 1 7 5 1 7 m 2 8 1 F w / w5 5 7 . 5 2 . 0 1 2 0 0 % 3 2 3 9 1 1 1 b a t / 0 0 7 . 0 5 7 . 6 . 1 . 1 . 7 0 g 8 6 5 8 7 5 7 m 3 2 1 8 1 8 1 . F n w o / 5 5 0 i t w5 3 7 . 2 . 0 1 1 2 0 a l % 2 3 9 1 1 u mr b o a t / 0 7 . 1 f g 0 3 4 6 0 6 7 . 9 . 3 . h 1 5 8 2 . 4 7 5 c a 96 m 2 4 8 e 1 n i F w d / w5 9 . 6 . 0 5 5 e . 0 0 s u % 3 0 3 8 1 1 0 1 s t n b e i at / 0 4 . 2 . 7 1 . p i g 0 3 0 9 8 6 . 5 6 c 8 . 8 3 . 4 7 5 x 86 m 2 1 8 e c 1 i F f i w / 9 c . 6 0 e w5 % 3 3 . 3 9 1 0 1 1 5 . 0 0 1 p s r o f # n o i t l e a n a 1 a 2 t 9 6 a n at e l a a i r o ul e l t o r t n t n r e a r g n a c l a t b a ma o e e d r mu li u li n i e t n i i r b o T T o o Ma B F V D D s i u D L tr e f e # 1 2 3 3 4 5 a R
Table 69
[0707] Tablets having hardnesses of 3-4 kp, 5-8 kp, or 10-12 kp were prepared from Formulations F150-F158 and F167-F170. [0708] The dissolution profiles of the direct blend formulations and the tablets prepared from the formulations were studied using Non-Sink Dissolution Test Method 3. The results are shown in Tables 70-72. Table 70
Table 71
Table 72
Example 16: Vamorolone Oral Dosage Forms Prepared by Wet Granulation [0709] Formulations F124-F130 (see Tables 73-75 below) are prepared using the procedure described below and in FIG.8. [0710] 1. Weigh all the ingredients as per the pharmacy weighing sheet of the batch record. Adjust the quantity of vamorolone based on assay and water content. [0711] 2. Pre-blend: Add intra-granular 50% diluent to a high shear granulator and mix for 2 minutes, then add vamorolone followed by binder and remaining diluent (intragranular) and mix for 10 minutes. [0712] 3. Granulation: Granulate with solvent (water or ethanol or hydroalcoholic solution) and record the granulation parameters (solvent addition time, mixing time and product temperature). Determine the granulation end point based on the power consumption. Measure LOD of granules. Granulation solution can be prepared by dissolving the binder in the solvent or can be added in dry form. The quantity of the solvent is q.s. depending on the granulation end point. The solvent can be water, ethanol or hydroalcoholic solution. [0713] 4. Drying: Dry the wet granules in an oven by spreading the material on trays. Record the drying temperature, drying time and the LOD (NMT 2.0%). [0714] 5. Blending: After milling, transfer the milled granules to a PE bag. Add the extra granular disintegrant and mix for 12 minutes. [0715] 6. Lubrication: Screen the lubricant through a 30-mesh hand screen. Add the screened material to the PE bag and mix for 3 minutes. [0716] 7. Sampling from V blender (optional): Collect one to three unit-dose samples from 3 different locations of the PE bag using an appropriately sized sample thief.
Table 73
1Granulation solution can be water, ethanol or hydroalcoholic mixture. Table 74
1Granulation solution can be water, ethanol or hydroalcoholic mixture. Table 75
1Granulation solution can be water, ethanol or hydroalcoholic mixture. [0717] Tablets are prepared by compressing one of formulations F124-F130 according to specification in Table 76. Table 76
[0718] Capsules having the specifications in Table 77 are prepared by filling one of formulations F124-F130 into hard gelatin/HPMC capsules (using size 3 capsules for 150 mg fill weight and size 00 capsules for 500 mg fill weight).
Table 77
Example 16a: Vamorolone Oral Dosage Forms Prepared by Wet Granulation [0719] Formulations F159-F163 and F176-178 described in Tables 78-80 were prepared by wet granulation. [0720] Diluent was added to a PE bag and mixed, then vamorolone, additional diluent, and binder were added to the mixture and mixed. The mixture was transferred to a 500 mL beaker and mixed with solvent. The mixture was screened through a 20 mesh screen and air dried overnight. The dried granules were weighed and mixed with disintegrant in a PE bag. Lubricant was screened through a 30 mesh screen and added to the PE bag and mixed. The mixture was compressed into tablets using a Carver press. Table 78
Table 79
Table 80
[0721] Tablets having hardnesses of 5-7 kp or 10 kp were prepared from Formulations F159-F163. [0722] The dissolution profiles of the wet granulation formulations and the tablets prepared from the formulations were studied. The results are shown in Table 81.
Table 81
[0723] It is to be appreciated that the Detailed Description section, and not the Summary and Abstract sections, is intended to be used to interpret the claims. The Summary and Abstract sections may set forth one or more but not all exemplary embodiments of the present invention as contemplated by the inventor(s), and thus, are not intended to limit the present invention and the appended claims in any way. [0724] The present disclosure has been described above with the aid of functional building blocks illustrating the implementation of specified functions and relationships thereof. The boundaries of these functional building blocks have been arbitrarily defined herein for the convenience of the description. Alternate boundaries can be defined so long as the specified functions and relationships thereof are appropriately performed. [0725] The foregoing description of the specific embodiments will so fully reveal the general nature of the invention that others can, by applying knowledge within the skill of the art, readily modify and/or adapt for various applications such specific embodiments, without undue experimentation, without departing from the general concept of the present invention. Therefore, such adaptations and modifications are intended to be within the meaning and range of equivalents of the disclosed embodiments, based on the teaching and guidance presented herein. It is to be understood that the phraseology or terminology herein is for the purpose of description and not of limitation, such that the terminology or phraseology of the present specification is to be interpreted by the skilled artisan in light of the teachings and guidance. [0726] The breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents. [0727] The claims in the instant application are different than those of the parent application or other related applications. The Applicant therefore rescinds any disclaimer of claim scope made in the parent application or any predecessor application in relation to the instant application. The Examiner is therefore advised that any such previous disclaimer and the cited references that it was made to avoid, can need to be revisited.
Further, the Examiner is also reminded that any disclaimer made in the instant application should not be read into or against the parent application.