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US20070071813A1 - Novel dosage formulation - Google Patents

Novel dosage formulation Download PDF

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Publication number
US20070071813A1
US20070071813A1 US11/524,981 US52498106A US2007071813A1 US 20070071813 A1 US20070071813 A1 US 20070071813A1 US 52498106 A US52498106 A US 52498106A US 2007071813 A1 US2007071813 A1 US 2007071813A1
Authority
US
United States
Prior art keywords
lower alkyl
hydrogen
hot melt
group
sulfur
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11/524,981
Other languages
English (en)
Inventor
Hashim Ahmed
Susanne Page
Navnit Shah
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=37671050&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20070071813(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Individual filed Critical Individual
Priority to US11/524,981 priority Critical patent/US20070071813A1/en
Publication of US20070071813A1 publication Critical patent/US20070071813A1/en
Priority to US12/954,970 priority patent/US20110070303A1/en
Priority to US13/787,870 priority patent/US8852634B2/en
Abandoned legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient

Definitions

  • Some examples of how foods and drugs can interact include:
  • Food can speed up or slow down the action of a medication.
  • Drugs may alter how nutrients are used in the body.
  • NK-1 receptor antagonists of formula I have been described in commonly owned EP 1,035,115 and U.S. Pat. No. 6,297,375 wherein
  • NK1 receptor antagonists useful for the treatment of CNS disorders, such as depression, anxiety and emesis.
  • bioavailability of a drug depends on several parameters, such as on the physicochemical nature of the active compound, the dosage form, and other physiological factors.
  • Compounds of formula I are virtually insoluble in water and simulated gastric fluid, inhibiting oral bioavailability.
  • the present invention provides new galenic compositions for oral administration of pharmaceutically active compounds and a new process for preparing such galenic compositions.
  • the compositions and process employ a hot melt extrusion of the active pharmaceutical ingredient and a poloxamer.
  • the invention further provides hot melt extrudates of an active pharmaceutical ingredient and a poloxamer.
  • oral dosage forms of the invention are suitable for delivery to human patients and are designed to enable sufficient availability of the active compound at its site of action. Such formulations may overcome the disadvantage of practical insolublility in simulated intestinal fluid for these compounds.
  • the process of the invention provides, in particular, a process for preparing a pharmaceutical tablet composition, wherein the active pharmaceutical ingredient of formula I or pharmaceutically acceptable acid addition salts thereof and a water soluble poloxamer are processed by hot melt extrusion before mixing with the other ingredients.
  • the tablet composition can thereafter be coated with a composition comprising an immediate release film coating system and purified water.
  • lower alkyl denotes a straight- or branched-chain alkyl group containing from 1 to 7 carbon atoms.
  • Nonlimiting examples of lower alkyl include methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, t-butyl, and the like.
  • alkylene group means a lower alkyl linker which is bound to a group at either end.
  • alkylene groups include methylene, ethylene, propylene, and the like.
  • lower alkoxy denotes a alkyl group as defined above, which is attached through an oxygen atom.
  • Nonlimiting examples of lower alkoxy groups include methoxy, ethoxy, propoxy, and the like.
  • cycloalkyl denotes a saturated carbocyclic group (e.g. a nonaromatic ring) containing 3 to 6 carbon atoms.
  • Nonlimiting examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.
  • halogen denotes chlorine, iodine, fluorine, and bromine.
  • “Processing aids” are excipients that improve the manufacturability of the formulation by improving, for instance, flowability and by avoiding sticking.
  • colloidal silicon dioxide is a submicroscopic fumed silica with a particle size of about 15 nm. It is a light, loose, bluish-white-colored, odorless, tasteless nongritty amorphous powder.
  • Nonlimiting examples of colloid silicon dioxides useful in the invention include Aerosil 380 and Cab-O-Sil.
  • a “tablet filler/diluent” is a material that improves the bulk properties, e.g. mixing, flow, and compression, of a pharmaceutical formulation. They fill out the size of a tablet or capsule, making it practical to produce and convenient for consumer use. By increasing the bulk volume, the final product has the proper volume for patient handling.
  • Nonlimiting examples of tablet filler/diluent include starch, modified starch derivatives, cellulose, calcium salts, sugar and sugar alcohols.
  • Starch is a substance consisting of amylase and amylopectin, two polysaccharides based on a-glucose.
  • One type of starch that can be used in the invention is corn starch.
  • corn starches Nonlimiting examples of corn starches that can be used in the invention include Pure-Cote, Pure-Bind, Pure-Dent, Pure-Gel, Pure-Set, Melojel, Meritena, Paygel55, Perfectamyl D6PH, Purity 21, Purity 826, and Tablet White.
  • MCC microcrystalline cellulose
  • CMOS complementary metal-oxide-semiconductor
  • CMOS complementary metal-oxide-semiconductor
  • Vivacel a naturally occurring polymer comprised of a glucose units connected by a 1-4 ⁇ glycosidic bond.
  • MCC can be derived from a special grade of alpha cellulose.
  • Nonlimiting examples of MCC that can be used in the invention include Avicel, Vivapur, Vivacel, Emcocel.
  • mannitol One type of sugar alcohol that can be used as tablet filler/diluent is mannitol.
  • mannitol Nonlimiting examples of mannitol that can be used in the invention include Parteck M 200.
  • a “disintegrant” is a material that enhances the disintegrating properties of a pharmaceutical formulation. Typically, disintegrants expand, swell, and dissolve when wet, causing the tablet to break apart in the digestive tract, releasing the active ingredients for absorption. Different types of disintegrants such as NVP water-swellable polymers, croscarmellose and cellulose derivatives can be used in the invention.
  • a “glidant” is a material used to improve the flowability of the powder or granules or both.
  • N-vinylpyrrolidone e.g. N-vinyl-2-pyrrolidone.
  • “Pharmaceutically acceptable acid addition salts” embraces salts with inorganic or organic acids, such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric acid, methane-sulfonic acid, p-toluenesulfonic acid and the like.
  • Water-soluble poloxamers are block copolymers of ethylene oxide ,i.e. polyoxyethylene (POE), and propylene oxide, i.e. polyoxypropylene (POP), that are soluble in water and are used as wetting agents in pharmaceutical formulations.
  • POE polyoxyethylene
  • POP polyoxypropylene
  • Nonlimiting examples of poloxamers useful in the present invention include Lutrol F68 (poloxamer 188).
  • Extrusion is the process of converting a raw material into a product of uniform shape and density by forcing it through a die under controlled conditions.
  • the present invention provides a composition which comprises a hot melt extrudate that comprises an active pharmaceutical ingredient and a water-soluble poloxamer.
  • the invention provides a composition which comprises a hot melt extrudate that comprises a compound of formula I and a water soluble poloxamer, for example Lutrol F68.
  • a preferred compound of formula I is the compound, 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide, having the structural formula and which exhibits the above noted insolubilities, i.e. ⁇ 0.0001 mg/ml in water and aqueous buffer solutions of pH 3.0-7.0.
  • the invention provides a composition
  • a hot melt extrudate that comprises a compound of formula I, such as 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramidehydrochloride and a water-soluble poloxamer, such as Lutrol F68.
  • a preferred form of the composition is a pharmaceutical tablet, such as a coated pharmaceutical tablet, in particular a 400 mg tablet.
  • the pharmaceutical tablet composition if the invention comprises a) an active ingredient of formula I 30-60% b) a water soluble poloxamer 10-20% c) a filler 20-30% d) a disintegrant 1-10% e) processing aid and 0-5% and f) glidant 0-5%, and if desired g) immediate release film coating system 2-5% of the tablet weight h) purified water
  • An example of a representative formulation composition comprises the ingredients 2-(3,5-Bis-trifluoromethyl-phenyl)- 400.00 N-methyl-N-(6-morpholin-4-yl- 4-o-tolyl-pyridin-3-yl)- isobutyramide hydrochloride Lutrol F68 133.35 Microcrystalline Cellulose(Avicel PH102) 162.65 Parteck M 200(Mannitol) 30.00 Polyplasdone XL 16.00 Colloidal Silicon Dioxide(Aerosil 380) 16.00 Corn Starch 30.00 Magnesium Stearate 12.00 Total Weight of Kernel 800.00 An example of a representative coating composition comprises Opadry Yellow 03K 12429 25.00 Purified Water 131.25 Total Weight of Film Coated Tablet 825.00
  • the present invention also provides the hot melt extrudate employed in the composition.
  • the extrudate comprises an active pharmaceutical ingredient and a poloxamer.
  • the hot melt extrudate comprises a compound of formula I or a pharmaceutically acceptable salt thereof and a poloxamer.
  • the invention provides an extrudate of 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramidehydrochloride and a water-soluble poloxamer, such as Lutrol F68.
  • HFME hot melt extrusion
  • the invention provides a process for the manufacture of an extrudate that comprises an active pharmaceutical ingredient and a poloxamer which comprises
  • Blending of the active pharmaceutical ingredient and the poloxamer can be accomplished in any conventional manner.
  • the two ingredients can be placed in a mixer or blender, for example, a PK Bin or Bohle mixer, and mixed.
  • a portion of the active pharmaceutical ingredient for example, about 50%, can be mixed with the poloxamer, followed by addition of the remainder of the active pharmaceutical ingredient.
  • the material is preferably mixed for a period of about 30 minutes.
  • the invention provides a process for preparing an extrudate comprising 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramidehydrochloride and Lutrol F68 which comprises blending 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramidehydrochloride with Lutrol F68 to form a powder blend, extruding the powder blend from step 1) to form a hot melt extrudate, and collecting the hot melt extrudate at room temperature.
  • the invention provides a process for preparation of an extrudate which comprises
  • the powder blend contains additional ingredients, such as a tablet binder and/or wettability agent.
  • additional ingredients such as a tablet binder and/or wettability agent.
  • the hot melt extrudate can be passed through a sieving machine to obtain milled material, whereby more than one sieving step may be necessary to obtain material in the desired particle size range.
  • the present invention further provides a process for preparing a pharmaceutical tablet composition which comprises:
  • the invention provides a process for preparing a pharmaceutical tablet composition which comprises:
  • the process comprises:
  • the kernels can be coated as follows:

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Otolaryngology (AREA)
  • Psychiatry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
US11/524,981 2005-09-23 2006-09-21 Novel dosage formulation Abandoned US20070071813A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US11/524,981 US20070071813A1 (en) 2005-09-23 2006-09-21 Novel dosage formulation
US12/954,970 US20110070303A1 (en) 2005-09-23 2010-11-29 Novel dosage formulation
US13/787,870 US8852634B2 (en) 2005-09-23 2013-03-07 Dosage formulation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US71979305P 2005-09-23 2005-09-23
US11/524,981 US20070071813A1 (en) 2005-09-23 2006-09-21 Novel dosage formulation

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/954,970 Continuation US20110070303A1 (en) 2005-09-23 2010-11-29 Novel dosage formulation

Publications (1)

Publication Number Publication Date
US20070071813A1 true US20070071813A1 (en) 2007-03-29

Family

ID=37671050

Family Applications (3)

Application Number Title Priority Date Filing Date
US11/524,981 Abandoned US20070071813A1 (en) 2005-09-23 2006-09-21 Novel dosage formulation
US12/954,970 Abandoned US20110070303A1 (en) 2005-09-23 2010-11-29 Novel dosage formulation
US13/787,870 Active US8852634B2 (en) 2005-09-23 2013-03-07 Dosage formulation

Family Applications After (2)

Application Number Title Priority Date Filing Date
US12/954,970 Abandoned US20110070303A1 (en) 2005-09-23 2010-11-29 Novel dosage formulation
US13/787,870 Active US8852634B2 (en) 2005-09-23 2013-03-07 Dosage formulation

Country Status (26)

Country Link
US (3) US20070071813A1 (zh)
EP (1) EP1928427B1 (zh)
JP (2) JP5523706B2 (zh)
KR (1) KR20080043852A (zh)
CN (2) CN103893145A (zh)
AR (1) AR056198A1 (zh)
AT (1) ATE453384T1 (zh)
AU (1) AU2006298898B2 (zh)
BR (1) BRPI0616108A2 (zh)
CA (1) CA2623237C (zh)
DE (1) DE602006011485D1 (zh)
DK (1) DK1928427T3 (zh)
ES (1) ES2335922T3 (zh)
HK (1) HK1198914A1 (zh)
HR (1) HRP20100111T1 (zh)
IL (1) IL189929A (zh)
MY (1) MY143784A (zh)
NO (1) NO340473B1 (zh)
NZ (1) NZ566419A (zh)
PL (1) PL1928427T3 (zh)
PT (1) PT1928427E (zh)
RU (1) RU2431473C2 (zh)
SI (1) SI1928427T1 (zh)
TW (1) TWI375572B (zh)
WO (1) WO2007039420A1 (zh)
ZA (1) ZA200802272B (zh)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100159003A1 (en) * 2007-06-12 2010-06-24 Ratiopharm Gmbh Process for the preparation of a medicament comprising vardenafil hydrochloride trihydrate
US20110028456A1 (en) * 2008-01-11 2011-02-03 Cipla Limited Solid Pharmaceutical Dosage Form
US20120114751A1 (en) * 2010-11-09 2012-05-10 Andreas Leiminer Pharmaceutical composition for treating hcv infections
CN104586770A (zh) * 2014-12-30 2015-05-06 山东博迈康药物研究有限公司 一种盐酸帕唑帕尼的热熔挤出制剂及其制备方法
WO2015068744A1 (ja) 2013-11-08 2015-05-14 キッセイ薬品工業株式会社 カルボキシメチルピペリジン誘導体
KR20170002474A (ko) 2014-05-07 2017-01-06 깃세이 야쿠힌 고교 가부시키가이샤 사이클로헥실피리딘 유도체
US10647705B2 (en) 2017-11-14 2020-05-12 Merck Sharp & Dohme Corp. Substituted biaryl compounds as indoleamine 2,3-dioxygenase (IDO) inhibitors
US11771655B2 (en) * 2014-09-08 2023-10-03 University Of Central Lancashire Solid dosage form production
US12539290B2 (en) 2024-04-30 2026-02-03 Eidos Therapeutics, Inc. Formulations of AG10

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK2774925T3 (en) 2005-11-08 2017-02-27 Vertex Pharma Heterocyclic modulators of ATP binding cassette transporters
US7671221B2 (en) 2005-12-28 2010-03-02 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
US7754739B2 (en) 2007-05-09 2010-07-13 Vertex Pharmaceuticals Incorporated Modulators of CFTR
AU2008251504B2 (en) 2007-05-09 2013-07-18 Vertex Pharmaceuticals Incorporated Modulators of CFTR
LT2225230T (lt) 2007-12-07 2017-01-25 Vertex Pharmaceuticals Incorporated 3-(6-(1-(2,2-difluorbenzo[d][1,3]dioksol-5-il) ciklopropankarboksamido)-3-metilpiridin-2-il) benzoinės rūgšties kietos formos
EP2639222B1 (en) 2007-12-07 2016-08-31 Vertex Pharmaceuticals Incorporated Process for producing cycloalkylcarboxiamido-pyridine benzoic acids
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