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WO2010092596A1 - Composition pharmaceutique orale de dutastéride - Google Patents

Composition pharmaceutique orale de dutastéride Download PDF

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Publication number
WO2010092596A1
WO2010092596A1 PCT/IN2010/000073 IN2010000073W WO2010092596A1 WO 2010092596 A1 WO2010092596 A1 WO 2010092596A1 IN 2010000073 W IN2010000073 W IN 2010000073W WO 2010092596 A1 WO2010092596 A1 WO 2010092596A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
dutasteride
oral pharmaceutical
surfactant
pharmaceutically acceptable
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.)
Ceased
Application number
PCT/IN2010/000073
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English (en)
Inventor
Deepak Murpani
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.)
GENEPHARM INDIA PRIVATE Ltd
Original Assignee
GENEPHARM INDIA PRIVATE Ltd
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
Application filed by GENEPHARM INDIA PRIVATE Ltd filed Critical GENEPHARM INDIA PRIVATE Ltd
Priority to EP10741016.9A priority Critical patent/EP2395975A4/fr
Publication of WO2010092596A1 publication Critical patent/WO2010092596A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
    • 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
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • 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
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/28—Antiandrogens

Definitions

  • the present invention relates to an oral composition of dutasteride.
  • Dutasteride a synthetic 4- azasteroid compound is an antiandrogen with the chemical name (5 ⁇ , 17 ⁇ ) -N- ⁇ 2, 5 bis (trifluoromethyl) phenyl ⁇ -3- oxo-4-azaandrost -l-ene-17- carboxamide.
  • Dutasteride is indicated for the treatment of symptomatic benign prostate hyperplasia (BPH) in men with enlarged prostate glands.
  • BPH benign prostate hyperplasia
  • Dutasteride a synthetic 4-azasteroid compound is a selective inhibitor of both the type 1 and type 2 isoforms of steroid 5 ⁇ -reductase (5AR), an intracellular enzyme that converts testosterone to 5 ⁇ -dihydrotestosterone (DHT).
  • 5AR steroid 5 ⁇ -reductase
  • DHT 5 ⁇ -dihydrotestosterone
  • Dutasteride is marketed as 0.5 mg strength soft gelatin capsules for oral administration by M/S Glaxo Smithkline Pharmaceuticals as Avodart. Each capsule contains 0.5 mg dutasteride dissolved in a mixture of mono-di-glycerides of caprylic/ capric acid (349.5mg) and butylated hydroxytoluence (0.035mg).
  • time to peak serum concentrations (Tmax) of dutasteride occurs within 2 to 3 hours. Absolute bioavailability in five healthy subjects is approximately 60% (range 40% to 94%). When the drug is administered with food, the maximum serum concentrations were reduced by 10% to 15%.
  • the marketed soft gelatin capsules have the following drawbacks.
  • the capsule consists of an oily solution of dutasteride.
  • oily solution of dutasteride.
  • biovailability of oily solution depends on many biopharmaceutical variables the bioavailability may be variable.
  • Lipid based formulation is beautifully classified by Pouton into three broad categories: Type I - Simple solution of Active in Triglycerides and/or mixed glycerides (e.g. Avodart) Type II - Active + Triglycerides and/or mixed glycerides + lipophilic surfactant (HLB ⁇ 12) Type III - Active + Triglycerides and/or mixed glycerides + Hydrophilic surfactant + co-solvent (yielding SMEDDS formulation)
  • SMEDDS Self Microemulsifying Drug Delivery system
  • aqueous media e.g. 0.1 N HCl, Water, pH 4.5 buffer, pH 6.8 buffer (mimicking the GIT fluid pH) can result in a ME.
  • Microemulsion can serve as a very effective dosage form to improve to therapeutic effectiveness of growing number of poorly soluble drugs, both for oral and parenteral route. It has been shown in many cases to significantly increase bioavailability of poorly soluble drugs and also known to improve the inter and intra subject variability, fed/ fasting state bioavailability.
  • Microemulsions is dispersions of oily phase in aqueous phase -o/w ME or vice-versa. The droplet size of dispersed phase below 200 nm makes it transparent or almost transparent (sometimes with bluish tinge).
  • SMEDDS are suitable to be filled in soft gelatin capsule.
  • Hard capsules Gelatin or Non-Gelatin. Conversion of an oily liquid to solid free flowing/ compressible powder is also been increasingly explored.
  • the object of the present invention is to provide dutasteride in a form which may be filled in capsules or converted into powder which may be compressed into pellets or tablets or directly filled in capsules.
  • the present invention provides an oral pharmaceutical composition of dutasteride or its pharmaceutically acceptable salt and the process of its preparation.
  • An oral pharmaceutical composition of dutasteride or its pharmaceutically acceptable salt comprising admixture of a) dutasteride or its pharmaceutically acceptable salt ; b) one or more surfactant (s) /co-surfactant (s); c) one or more oil (s); d) optionally antioxidant (s); and e) optionally excipient (s) ; wherein the composition upon dilution with aqueous medium forms microemulsion with atleast 95% particles having mean particle size below 200 nm.
  • a process for the preparation of an oral pharmaceutical composition of dutasteride or its pharmaceutically acceptable salt comprising mixing. a) dutasteride or its pharmaceutically acceptable salt ; b) one or more surfactant (s) /co-surfactant(s) ; c) one or more oil (s); d) optionally antioxidant (s); and e) optionally excipient (s) ; at ambient temperature or heating at 25-75 0 C for less than an hour and cooling to ambient temperature followed by filling in capsules or adsorbing on suitable adsorbent and compressed into pellets or tablets or filled into capsules.
  • the present invention relates to oral pharmaceutical composition of dutasteride or its pharmaceutically acceptable salt which is an admixture of dutasteride or its pharmaceutically acceptable salt, one or more surfactant (s)/ co-surfactant (s), one more oil (s),optionally antioxidant (s) and excipient (s).
  • the admixture may be filled in capsules or adsorbed on a suitable adsorbent to form a free-flowing powder which may be filled in capsules or compressed into pellets or tablets.
  • the oral pharmaceutical composition of the present invention in unabsorbed liquid form upon dilution with aqueous medium forms microemulsion with atleast 95% particles having mean particle size below 200nm.
  • Dutasteride is a poorly soluble white to pale yellow powder with its solubility being 0.38 ng/ml in water in water which is below the quantitation limit of the assay. Due to its low solubility it has a correspondingly low degree of bioavailability. Bioavailability of dutasteride or pharmaceutically acceptable salt may be improved by i. Milling /nanonising dutasteride or its pharmaceutically acceptable salt or ii. Dissolving or suspending dutasteride or its pharmaceutically acceptable salt in early stages of production.
  • dutasteride or its pharmaceutically accepted salt generates dust which is hazardous for working personnel.
  • Dissolving dutasteride in solvent like caprylic/capric acid could result in improved bioavailability but it requires very large quantities of solvents such as 349.5 mg for 0.5mg dutasteride.
  • dutasteride or its pharmaceutically acceptable salt when mixed with surfactant (s) / co-surfactant (s) ; oil(s), optionally antioxidant (s) and excipient (s) provides an oral composition which on dissolution with an aqueous medium forms micro emulsion with at least 95% particles having mean particles size below 200nm.
  • dutasteride with surfactant (s), oil(s), optional antioxidant (s) and excipient (s) may be admixture of dutasteride with surfactant (s), oil(s), optional antioxidant (s) and excipient (s)
  • an oral pharmaceutical composition of dutasteride or its pharmaceutically acceptable salt comprising admixture of dutasteride or its pharmaceutically acceptable salt; one or more surfactant (s) / co-surfactant(s); one or more oil (s); optionally antioxidant (s); and optionally excipient (s).
  • the admixture may be used as such or filled in capsules or adsorbed on adsorbent and compressed into pellets or tablets or filled in capsules.
  • dutasteride as used herein includes pharmaceutically acceptable salts or solvates and can be in crystalline phase, amorphous phase or a mixture thereof.
  • capsule as used herein includes soft / hard gelatin or hard non-gelatin capsules.
  • Surfactants utilized in the present invention possess an HLB (hydrophilic-lipophilic balance) number greater than 8 based on the HLB system which is well known to those skilled in the art.
  • the HLB number provides a means for ranking surfactants based on the balance between the hydrophilic and lipophilic portions of the surfactant or emulsifying agent. That is, the higher the HLB number, the more hydrophilic the surfactant or emulsifying agent.
  • the surfactant has a hydrophilic-lipophilic balance (HLB) of greater than 8.
  • HLB hydrophilic-lipophilic balance
  • surfactants within HLB in the range of 8-18 form oil/water emulsions.
  • the preferred HLB range for the surfactant is between approximately 10 and 14.
  • composition can also include the addition of an aqueous solvent such as triacetin, an acetylated derivative of glycerol, i.e., glyceryl triacetate or other suitable solvents.
  • an aqueous solvent such as triacetin, an acetylated derivative of glycerol, i.e., glyceryl triacetate or other suitable solvents.
  • Triacetin is suitable since it is miscible in the oil/lipid phase and can be used to solubilize a hydrophobic drug.
  • the oil selected for the oral pharmaceutical composition of the present invention has HLB value below 6 for e.g.
  • Triglycerides of fractionated vegetable C8 and ClO fatty acids usually fractionated coconut oil.
  • the relative proportions of surfactant and co-surfactant in the composition, formulation of the present invention can influence the solubilizing and dissolution properties of the formulation.
  • the range of concentration of the surfactant/ co-surfactant broadly ranges from 15 to 96% (v/v) and more preferably ranges from approximately from 30 to 90% (v/v).
  • the concentration of the co-surfactant broadly ranges from 10 to 80% (v/v).
  • the oil content in the oral composition of the present invention ranges from 4-60%, more preferably 4-44%.
  • the antioxidant used in oral composition of the present invention may be selected from butylated hydroxytoluence, butylated hydroxyl anisole, ⁇ -tocopherol ascorbic acid , ascorbyl palmitate sodium ascorbate, vitamin E, tartaric acid and the like.
  • the excipient used in oral composition of the present invention may be selected from diluents, binders lubricants, disintegrants, flavoring agents, coloring agents, stabilizers, glidants, plasticizers, preservatives and sweeteners.
  • the adsorbent used in oral composition of the present invention may be selected from kaolin, bentonite, hectorite, colloidal magnesium aluminium silicate, silicon dioxide, magnesium trisilicate, aluminium hydroxide magnesium oxide, talc, calcium - aluminium silicate, lactose.
  • Diluents may be selected from calcium-aluminum silicates (Sipernat 106 PQ), calcium carbonate,calcium phosphate dibasic, calcium phosphate tribasic, calcium sulfate, microcrystalline cellulose,microcrystalline silicified cellulose,powdered cellulose, dextrates, dextrose,fructose,lactitol,lactose anhydrous, lactose monohydrate,lactose dihydrate, lactose trihydrate,mannitol sorbitol, starch, pregelatinized starch ,sucrose,talc,xylitol,maltose maltodextrin,maltitol .
  • Binders may be selected from acacia, alginic acid, carbomer,carboxymethylcellulose calcium, carbomethylcellulose sodium,microcrystalline cellulose,powdered cellulose, ethyl cellulose, gelatin liquid glucose, guar gum, hydroxyethyl cellulos, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, maltodextrin,methylcellulose,ploydextrose, polyethtylene oxide,povidone,sodium alginate, starch paste, pregelatinized starch, sucrose, tragacanth, low-substituted hydroxypropyl cellulose,glucose, sorbitol.
  • Suitable fillers are preferably selected from atleast one of starch derivatives,such as corn starch, potato starch or rice starch.
  • starch derivatives such as corn starch, potato starch or rice starch.
  • Polysaccharides such as dextrins, maltodextrins, dextrates, microcrystalline cellulose, powdered cellulose, mixture of microcrystalline cellulose and guar gum, coprocessed blends of microcrystalline cellulose; and polyhydric alcohols, such as xylitol and sorbitol.
  • Disintegrants may for example, example, alginic acid, carbon dioxide, carbonxymethylcellulose calcium carboxymethylcellulose sodium, microcrystalline cellulose, powdered cellulose, croscarmelose sodium, crospovidone, sodium docusate, gaur gum, hydroxypropyl cellulose, methylcellulose, polacrilin potassium , poloxamer, povidone, sodium alginate, sodium glycine carbonate, sodium laulyl sulfate, sodium starch glycolate, starch, pregelatinized starch, low- substituted hydroxypropyl cellulose.
  • Glidants may be , for example, calcium silicate, powdered cellulose, starch, talc, colloidal silicon dioxide.
  • Lubricants may be selected from magnesium stearate, stearic acid, sodium stearyl fumarate, magnesium lauryl sulphate, talc, polyethylene glycol, and glyceryl behenate.
  • Suitable sweeteners may be selected from sugars such as sucrose, lactose and glucose; cyclamate and salts thereof; saccharin and salts thereof; and aspartame.
  • Flavouring agents may be selected from natural or synthetic flavours such as strawberry flavour, wild cherry flavour, green apple flavour, spearmint flavour and peppermint flavour.
  • a process for the preparation of an oral pharmaceutical composition of dutasteride or its pharmaceutically acceptable salt comprising mixing. a) dutasteride or its pharmaceutically acceptable salt ; b) one or more surfactant (s) / co-surfactant (s) ; c) one or more oil (s); d) optionally antioxidant (s); and e) optionally excipient (s) ; at ambient temperature or heating at 25-75 0 C for less than an hour and cooling to ambient temperature.
  • the oral pharmaceutical composition of the present invention upon dilution with aqueous medium forms microemulsion with at least 95% particles having mean particle size below 200nm.
  • the admixture may be used as such or filled in capsules or adsorbed on an adsorbent and compressed into pellet or tablets or filled in capsules.
  • a process for the preparation of an oral pharmaceutical composition of dutasteride or its pharmaceutically acceptable salt comprising mixing, a) dutasteride or its pharmaceutically acceptable salt ; one or more surfactant (s)/ co-surfactant(s); c) one or more oil (s); d) optionally antioxidant (s); and e) optionally excipient (s) ; at ambient temperature or heating at 25-75 0 C for less than an hour and cooling to ambient temperature followed by filling in capsules or adsorbing on suitable adsorbent and filling in capsules or compressing into pellet or tablets.
  • the oral pharmaceutical composition of the present invention wherein the liquid composition, before adsorption on solid, upon dilution with aqueous medium forms microemulsion with at least 95% particles having mean particle size below 200nm.
  • PROCEDURE (Example 1-4) :
  • EXAMPLE- 8 and 9 EXAMPLE 10 CONTROL FORMULATON, WET GRANULATION:
  • EXAMPLE 11 DISSOLUTION and GLOBULE SIZE COMPARISON OF ZERO DAY SAMPLE WITH AVODART
  • EXAMPLE 12 DISSOLUTION and GLOBULE SIZE COMPARISON OF 3MONTH ACCELERATED STABILITY STUDY SAMPLE AT 40° C/75% RH
  • EXAMPLE 13 DISSOLUTION COMPARISON OF ZERO DAY SAMPLES WITH AVODART

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Abstract

La présente invention concerne une composition pharmaceutique orale de dutastéride ou son sel pharmaceutiquement acceptable, comprenant un mélange des éléments suivants : a) un dutastéride ou son sel pharmaceutiquement acceptable; b) un ou plusieurs surfactants/co-surfactants; c) une ou plusieurs huiles(s); d) éventuellement un ou des antioxydants; et e) éventuellement un ou des excipients. Ladite composition, lors de sa dilution dans un milieu aqueux, forme une microémulsion dont au moins 95 % de particules présentent une taille de particule moyenne inférieure à 200 nm.
PCT/IN2010/000073 2009-02-10 2010-02-10 Composition pharmaceutique orale de dutastéride Ceased WO2010092596A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP10741016.9A EP2395975A4 (fr) 2009-02-10 2010-02-10 Composition pharmaceutique orale de dutastéride

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN278/MUM/2009 2009-02-10
IN278MU2009 2009-02-10

Publications (1)

Publication Number Publication Date
WO2010092596A1 true WO2010092596A1 (fr) 2010-08-19

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PCT/IN2010/000073 Ceased WO2010092596A1 (fr) 2009-02-10 2010-02-10 Composition pharmaceutique orale de dutastéride

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EP (1) EP2395975A4 (fr)
WO (1) WO2010092596A1 (fr)

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102166270A (zh) * 2011-04-06 2011-08-31 西北农林科技大学 一种水包油型陈皮油纳米乳及其制备方法
EP2395975A1 (fr) 2009-02-10 2011-12-21 Genepharm India Private Limited Composition pharmaceutique orale de dutastéride
WO2012076516A1 (fr) 2010-12-06 2012-06-14 Krka, Tovarna Zdravil, D.D., Novo Mesto Compositions pharmaceutiques comprenant du dutastéride
WO2013074205A1 (fr) * 2011-11-17 2013-05-23 Mylan Inc. Formulations pharmaceutiques en capsule de gel dure remplie de liquide
CN103169712A (zh) * 2011-12-20 2013-06-26 重庆华邦制药有限公司 提高生物利用度的度他雄胺制剂及其制备方法
KR20130086551A (ko) * 2012-01-25 2013-08-02 한미약품 주식회사 두타스테라이드 함유 자가 유화 약물전달 시스템용 조성물 및 이의 제조 방법
WO2014002015A1 (fr) * 2012-06-25 2014-01-03 Ranbaxy Laboratories Limited Composition pharmaceutique comprenant du dutastéride
CN103655470A (zh) * 2012-09-18 2014-03-26 重庆医药工业研究院有限责任公司 一种度他雄胺自微乳组合物及其制备方法
WO2014147096A1 (fr) * 2013-03-19 2014-09-25 Galenicum Health S.L. Compositions pharmaceutiques comprenant un principe actif
CN104069084A (zh) * 2013-03-25 2014-10-01 重庆华邦制药有限公司 一种质量稳定的度他雄胺软胶囊
CN104146966A (zh) * 2013-05-15 2014-11-19 重庆医药工业研究院有限责任公司 一种度他雄胺自微乳冻干组合物及其制备方法
WO2014209062A1 (fr) 2013-06-28 2014-12-31 Hanmi Pharm. Co., Ltd. Formule de capsule molle orale comprenant du dutastéride
US20150004104A1 (en) * 2012-03-02 2015-01-01 Colgate-Palmolive Company Oral care compositions
EP2837379A1 (fr) 2013-08-12 2015-02-18 Ems S.A. Forme posologique comprenant un inhibiteur de stéroïdes de la 5-alpha-reductase et bloqueur alpha, procédé de préparation d'une forme posologique, utilisation d'une forme posologique, procédé de traitement ou de prophylaxie d'une maladie ou condition induite par un androgène
EP2949319A1 (fr) 2014-05-26 2015-12-02 Galenicum Health S.L. Compositions pharmaceutiques comprenant un agent actif
WO2016114521A1 (fr) * 2015-01-14 2016-07-21 동아에스티 주식회사 Composition de dutastéride sous forme de comprimé présentant une stabilité améliorée
KR101679992B1 (ko) * 2015-12-31 2016-11-28 주식회사 유유제약 프로필렌글리콜 모노라우레이트를 포함하는 두타스테리드의 약학적 조성물 및 이의 제조 방법
US20170014382A1 (en) * 2015-04-10 2017-01-19 Bioresponse, L.L.C. Self-emulsifying formulations of dim-related indoles
JP2017503866A (ja) * 2014-12-23 2017-02-02 ハンミ ファーム． シーオー．， エルティーディー． デュタステリドを含む自己乳化型薬物送達システムのための組成物
WO2017043913A1 (fr) * 2015-09-10 2017-03-16 Yuyu Pharma, Inc. Composition pharmaceutique comprenant du dutastéride et formulation en gélule la comprenant
CN109310643A (zh) * 2016-05-12 2019-02-05 株式会社柳柳制药 含甘油脂肪酸酯衍生物或丙二醇脂肪酸酯衍生物的度他雄胺和他达拉非复合制剂及包含其的口服胶囊制剂
CN109843272A (zh) * 2016-09-30 2019-06-04 株式会社柳柳制药 度他雄胺和他达拉非的口服胶囊复合制剂
CN111388441A (zh) * 2018-12-13 2020-07-10 昆明积大制药股份有限公司 度他雄胺软胶囊
EP3738582A4 (fr) * 2018-01-10 2021-03-17 Shanghai WD Pharmaceutical Co., Ltd Particule solide, son procédé de préparation et composition pharmaceutique contenant des particules solides
KR20210092055A (ko) * 2020-01-15 2021-07-23 한국프라임제약주식회사 두타스테리드를 포함하는 경구용 약제학적 조성물
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EP2837379A1 (fr) 2013-08-12 2015-02-18 Ems S.A. Forme posologique comprenant un inhibiteur de stéroïdes de la 5-alpha-reductase et bloqueur alpha, procédé de préparation d'une forme posologique, utilisation d'une forme posologique, procédé de traitement ou de prophylaxie d'une maladie ou condition induite par un androgène
EP2949319A1 (fr) 2014-05-26 2015-12-02 Galenicum Health S.L. Compositions pharmaceutiques comprenant un agent actif
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US10799479B2 (en) 2015-04-10 2020-10-13 Bioresponse, L.L.C. Self-emulsifying formulations of DIM-related indoles
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CN108135914A (zh) * 2015-09-10 2018-06-08 株式会社柳柳制药 包含度他雄胺的药物组合物和包含其的胶囊制剂
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JP2019500416A (ja) * 2015-12-31 2019-01-10 ユーユー ファーマ，インコーポレーテッド デュタステリド及びプロピレングリコールモノラウレートを含有する医薬組成物及びその調製方法
CN109310643A (zh) * 2016-05-12 2019-02-05 株式会社柳柳制药 含甘油脂肪酸酯衍生物或丙二醇脂肪酸酯衍生物的度他雄胺和他达拉非复合制剂及包含其的口服胶囊制剂
CN109843272A (zh) * 2016-09-30 2019-06-04 株式会社柳柳制药 度他雄胺和他达拉非的口服胶囊复合制剂
EP3738582A4 (fr) * 2018-01-10 2021-03-17 Shanghai WD Pharmaceutical Co., Ltd Particule solide, son procédé de préparation et composition pharmaceutique contenant des particules solides
US11771690B2 (en) 2018-01-10 2023-10-03 Shanghai Wd Pharmaceutical Co., Ltd Solid particle, preparation method therefor, and pharmaceutical composition containing solid particle
CN111388441A (zh) * 2018-12-13 2020-07-10 昆明积大制药股份有限公司 度他雄胺软胶囊
KR20210092055A (ko) * 2020-01-15 2021-07-23 한국프라임제약주식회사 두타스테리드를 포함하는 경구용 약제학적 조성물
KR102352888B1 (ko) * 2020-01-15 2022-01-18 한국프라임제약주식회사 두타스테리드를 포함하는 경구용 약제학적 조성물
WO2022035003A1 (fr) * 2020-08-14 2022-02-17 (주)필인터내셔널 Composition pharmaceutique comprenant du dutastéride

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