WO2005066196A1 - Forme amorphe de finasteride et procede de preparation associe - Google Patents

Forme amorphe de finasteride et procede de preparation associe Download PDF

Info

Publication number
WO2005066196A1
WO2005066196A1 PCT/IB2004/004270 IB2004004270W WO2005066196A1 WO 2005066196 A1 WO2005066196 A1 WO 2005066196A1 IB 2004004270 W IB2004004270 W IB 2004004270W WO 2005066196 A1 WO2005066196 A1 WO 2005066196A1
Authority
WO
WIPO (PCT)
Prior art keywords
finasteride
process according
amorphous form
solution
solvent
Prior art date
Application number
PCT/IB2004/004270
Other languages
English (en)
Inventor
Yatendra Kumar
Saridi Madhava Dileep Kumar
Rakesh Singh
Swargam Sathyanarayana
Original Assignee
Ranbaxy Laboratories Limited
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 Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Publication of WO2005066196A1 publication Critical patent/WO2005066196A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
    • C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
    • C07J73/005—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by nitrogen as hetero atom
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • 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 amorphous form of finasteride and processes for its preparation.
  • the present invention also relates to pharmaceutical compositions that include amorphous finasteride.
  • Background of the Invention Chemically, finasteride is 17 ⁇ -N- (tert-butylcarbamoyl)-4-aza-5 ⁇ -androst-l-ene-3- one of structural Formula I
  • Formula I is l ⁇ iown from U.S. Patent No. 4,760,071. It is a testosterone 5 ⁇ -reductase inhibitor and is used in the treatment of hyperandro genie conditions, such as acne vulgaris, seborrhea, female hirsutism and benign prostatic hypertrophy.
  • Finasteride has been reported to exist in two crystalline polymorphic forms, I and II, in U.S. Patent Nos. 5,652,365 and 5,886,184 respectively.
  • Another polymorphic form, form III is disclosed in PCT application WO 02/20553. Summary of the Invention In one general aspect there is provided an amorphous form of finasteride.
  • the amorphous form of finasteride is characterized by the X-ray diffraction pattern as shown in figure 1.
  • a process for the preparation of an amorphous form of finasteride includes obtaining a solution of finasteride in one or more solvents and recovering the pure amorphous form of finasteride by the removal of the solvent.
  • Embodiments of the process may include one or more of the following features.
  • the solution of finasteride may be obtained directly from a reaction mixture or it may be obtained by dissolving crystalline finasteride in a solvent.
  • the solvent may include one or more of alcohols, ketones, ethers, chlorinated hydrocarbons, esters, nitriles, dipolar aprotic solvents, cyclic ethers and mixtures thereof.
  • the alcohols may include one or more of methanol, ethanol, isopropanol and mixtures thereof.
  • the chlorinated hydrocarbons may include one or more of dichloromethane, dichloroethane and mixtures thereof.
  • the nitriles may include one or more of acetonitrile and benzonitrile.
  • the cyclic ethers may include one or more of tetrahydrofuran, dioxane and mixtures thereof.
  • the ethers may include one or more of diethyl ether, diisopropylether, tertiary butylethylether and mixtures thereof.
  • the solvent may be removed by one or more of distillation, distillation under vacuum, evaporation, spray drying, freeze-drying, lyophilization, filtration, filtration under vacuum, decantation and centrifugation.
  • the amorphous form of finasteride may be recovered from the solution by spray drying.
  • the gas inlet temperature of the spray drier may range from about 40°C to about 100°C and the gas outlet temperature of the spray drier may range from about 20°C to about 80°C.
  • the process may further include adding one or more additional solvents before removing the solvent.
  • the one or more additional solvents may include organic solvents in which finasteride is insoluble, poorly soluble, practically insoluble or partially soluble.
  • the amorphous form of finasteride may be recovered from the solution by distillation.
  • the distillation may be carried out under vacuum.
  • the amorphous form of finasteride may also be recovered from the solution by filtration.
  • the process may further include drying of the product obtamed.
  • the amorphous finasteride obtained may have the X-ray diffraction pattern of Figure 1.
  • a process for the preparation of an amorphous form of finasteride includes subjecting crystalline finasteride to milling until the crystalline form is converted to the amorphous form.
  • Embodiments of the process may include one or more of the features described above.
  • a pharmaceutical composition comprising an amorphous form of finasteride and one or more pharmaceutically acceptable excipients.
  • Embodiments of the pharmaceutical composition may include one or more of the following features or those described above.
  • the pharmaceutical composition may further include one or more additional therapeutic ingredients.
  • the amorphous form of finasteride has the X-ray diffraction pattern as shown in figure 1.
  • a method of treating and preventing hyperandrogenic conditions including acne vulgaris, seborrhea, androgenetic alopecia, female hirsutism, and benign prostatic hypertrophy. The method mcludes administering a pharmaceutical composition of finasteride to a patient in need thereof, wherein the pharmaceutical composition includes an amorphous form of finasteride and one or more pharmaceutically acceptable excipients.
  • Fig. 1 is an X-ray diffraction spectrum of the amorphous form of finasteride.
  • Fig. 2 is an IR spectrum of the amorphous form of finasteride using potassium bromide pellets.
  • Fig. 3 is a DSC graph of the amorphous form of finasteride.
  • the amorphous form of finasteride is characterized by its non-crystalline nature. It may be characterized by X-ray powder diffraction spectrum, IR spectrum or DSC graph as shown in Figures 1, 2 and 3, respectively.
  • the inventors have developed a process for the preparation of the amorphous form of finasteride. The process includes obtaining a solution of finasteride in one or more of solvents and recovering the amorphous form of finesteride by the removal of the solvent.
  • the inventors also have developed pharmaceutical compositions that include the amorphous form of finesteride and one or more pharmaceutically acceptable excipients.
  • the solution of finasteride may be obtained by dissolving crystalline finasteride in one or more suitable solvents.
  • This solution of finasteride may be obtained directly from the last step of a reaction in which finasteride is formed.
  • the solution of crystalline finasteride may be obtamed by heating the solvent which includes crystalline finasteride. It may be heated from about 40°C to about 200°C, or from about 50°C to about 150°C. It may be heated for about 10 minutes to about 24 hours and, in particular, it may be heated for about 2 hours to about 3 hours. The solution may then be filtered to remove any undissolved foreign particulate matter.
  • the crystalline finasteride used as the starting material includes polymorphic forms I to III l ⁇ iown in the prior art, solvates, hydrates and mixtures thereof. Finasteride may be obtained by methods known in the art, such as the processes reported in U.S. Patent Nos.
  • the solvent may be removed by one or more of distillation, distillation under vacuum, evaporation, spray drying, freeze-drying, lyophilization, filtration, filtration under vacuum, decantation and centrifugation.
  • the amorphous form of finasteride maybe recovered, for example, from the solution by the spray drying technique.
  • the spray drying may be accomplished using a spray dryer that operates on the principle of nozzle spraying in a parallel flow, i.e., the sprayed product and the drying gas flow in the same direction.
  • the drying gas may be air or inert gases, such as nitrogen, argon and carbon dioxide.
  • the drying gas may be nitrogen.
  • the gas inlet temperature to the spray drier may range from about 40°C to about 100°C and the outlet temperature may range from about 20°C to about 80°C.
  • Suitable solvents include any solvent or solvent mixture in which finasteride is soluble.
  • This m cludes one or more of alcohols, ethers, esters, ketones, chlorinated hydrocarbons, nitriles, polar aprotic solvents, cyclic ethers, and mixtures thereof.
  • Suitable alcohols include one or more of methanol, ethanol, n-propanol, and isopropanol.
  • Suitable ketones include one or more of acetone, ethyl methyl ketone, methyl isobutyl ketone and diisobutyl ketone.
  • Suitable esters include one or more of ethyl formate, methyl acetate, ethyl acetate, isopropyl acetate, n-propyl acetate, isobutyl acetate, butyl acetate and amyl acetate.
  • Suitable ethers include one or more of diethylether, diisopropylether and tertiary butylethylether.
  • Suitable chlorinated hydrocarbons include methylene chloride and ethylenedichloride.
  • Suitable cyclic ethers include tetrahydrofuran and 1,4-dioxane.
  • Suitable polar aprotic solvents include one or more of N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulphoxide, acetonitrile and N-methylpyrrolidone.
  • Suitable nitriles include acetonitrile and benzonitrile.
  • the amorphous finasteride also can be recovered from the solution by freeze-drying.
  • the amorphous form of finasteride also can be recovered from the solution by adding a suitable second solvent resulting in the precipitation of the amorphous form. The second solvent is then removed by filtration, filtration under vacuum, decantation or centrifugation.
  • the second solvent may include organic solvents in which finasteride is insoluble, poorly soluble, practically insoluble or partially soluble and would be known to a person of ordinary skills in the art.
  • Suitable second solvents include one or more of cyclopentane, cyclohexane, cycloheptane, hexane, heptane, petroleum ether, water and mixtures thereof.
  • the process may further include drying the product obtained to achieve the desired moisture values. For example, the product may be dried in a tray drier, under vacuum or in a fluid bed dryer. Also provided is a process for the preparation of the amorphous form of finasteride.
  • the process includes subjecting crystalline finasteride or a slurry of finasteride in a solvent to milling until the crystalline form is converted to the amorphous form.
  • the slurry of the crystalline form in a solvent can be from about 30% to 85% w/v.
  • the milling may be carried out using a traditional technique of compounding, using a pestle and mortar, or by milling machines known in the art. Suitable milling machines include various makes of ball mills, roller mills, gyratory mills, and the like.
  • a pharmaceutical composition that includes the amorphous form of finasteride and one or more pharmaceutically acceptable excipients. This pharmaceutical composition also may include one or more additional therapeutic ingredients.
  • the amorphous form of finasteride may be conventionally formulated into tablets, capsules, suspensions, dispersions, injectables, creams, ointments, gels, solutions, transdermal patches, aerosols and other pharmaceutical forms. Any suitable route of administration may be employed including topical, peroral and parental. Also provided is a method for treating or preventing hyperandrogenic conditions, such as acne vulgaris, seborrhea, androgenetic alopecia, female hirsutism, and benign prostatic hypertrophy. The method includes administering a pharmaceutical composition that includes the amorphous form of finasteride and one or more pharmaceutically acceptable excipients.
  • the following example is intended to illustrate the invention should not be construed as limiting the scope of the invention in any way.
  • FT-IR Instrument Perkin Elmer, 16 PC SCAN: l ⁇ scans, 4.0 cm.-l according to the USP 25, general test methods page 1920, infrared absorption spectrum by potassium bromide pellet method.
  • Powder XRD, IR and DSC were similar to those shown in Figures 1, 2, and 3 respectively. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are included within the scope of the present invention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Steroid Compounds (AREA)

Abstract

L'invention concerne une forme amorphe de finastéride et leurs procédés de préparation. L'invention concerne également des compositions pharmaceutiques comprenant ledit finastéride amorphe.
PCT/IB2004/004270 2003-12-30 2004-12-23 Forme amorphe de finasteride et procede de preparation associe WO2005066196A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1642DE2003 2003-12-30
IN1642/DEL/2003 2003-12-30

Publications (1)

Publication Number Publication Date
WO2005066196A1 true WO2005066196A1 (fr) 2005-07-21

Family

ID=34746660

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2004/004270 WO2005066196A1 (fr) 2003-12-30 2004-12-23 Forme amorphe de finasteride et procede de preparation associe

Country Status (1)

Country Link
WO (1) WO2005066196A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014049071A1 (fr) * 2012-09-26 2014-04-03 Tangent Reprofiling Limited Modulateurs de la synthèse d'androgènes
US9585890B2 (en) 2012-09-26 2017-03-07 Tangent Reprofiling Limited Modulators of androgen synthesis

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0428366A2 (fr) * 1989-11-13 1991-05-22 Merck & Co. Inc. Procédé à déhydrogénation en position 1,2 des azasteroides
US6277391B1 (en) * 1998-06-05 2001-08-21 Samyang Corporation Composition and method of treating diseases and disorders of the prostate
WO2003029267A2 (fr) * 2001-09-29 2003-04-10 Ragactives, S.L. PROCEDE D'OBTENTION DE 17β-(SUBSTITUE)-3-OXO-Δ1,2-4-AZASTEROIDES ET INTERMEDIAIRES
KR20030042504A (ko) * 2001-11-23 2003-06-02 주식회사 중외제약 피나스테라이드 경구용 제제 및 그의 제조방법
WO2005000258A1 (fr) * 2003-06-27 2005-01-06 Amorepacific Corporation Nanoparticules polymeres auto-assemblees contenant des ingredients physiologiquement actifs et application externe contenant les nanoparticules

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0428366A2 (fr) * 1989-11-13 1991-05-22 Merck & Co. Inc. Procédé à déhydrogénation en position 1,2 des azasteroides
US6277391B1 (en) * 1998-06-05 2001-08-21 Samyang Corporation Composition and method of treating diseases and disorders of the prostate
WO2003029267A2 (fr) * 2001-09-29 2003-04-10 Ragactives, S.L. PROCEDE D'OBTENTION DE 17β-(SUBSTITUE)-3-OXO-Δ1,2-4-AZASTEROIDES ET INTERMEDIAIRES
EP1437361A2 (fr) * 2001-09-29 2004-07-14 Ragactives, S.L. Procede d'obtention de 17beta-(substitue)-3-oxo-delta 1,2-4-azasteroides et intermediaires
KR20030042504A (ko) * 2001-11-23 2003-06-02 주식회사 중외제약 피나스테라이드 경구용 제제 및 그의 제조방법
WO2005000258A1 (fr) * 2003-06-27 2005-01-06 Amorepacific Corporation Nanoparticules polymeres auto-assemblees contenant des ingredients physiologiquement actifs et application externe contenant les nanoparticules

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Section Ch Week 200377, Derwent World Patents Index; Class B01, AN 2003-826128, XP002318852 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014049071A1 (fr) * 2012-09-26 2014-04-03 Tangent Reprofiling Limited Modulateurs de la synthèse d'androgènes
US9072743B2 (en) 2012-09-26 2015-07-07 Tangent Reprofilling Limited Modulators of androgen synthesis
US9585887B2 (en) 2012-09-26 2017-03-07 Tangent Reprofiling Limited Modulators of androgen synthesis
US9585890B2 (en) 2012-09-26 2017-03-07 Tangent Reprofiling Limited Modulators of androgen synthesis
AU2013322612B2 (en) * 2012-09-26 2017-06-01 Tangent Reprofiling Limited Modulators of androgen synthesis
US9808462B2 (en) 2012-09-26 2017-11-07 Tangent Reprofiling Limited Modulators of androgen synthesis
US10111877B2 (en) 2012-09-26 2018-10-30 Tangent Reprofiling Limited Modulators of androgen synthesis
AU2017221819B2 (en) * 2012-09-26 2019-05-02 Tangent Reprofiling Limited Modulators of androgen synthesis

Similar Documents

Publication Publication Date Title
US20070191318A1 (en) Process for the preparation of amorphous rosuvastatin calcium
JP2022003038A (ja) リファキシミン
JP5149810B2 (ja) 無定形、無水結晶形または水和結晶形ドセタキセルの製造方法
JP2009197020A (ja) 薬剤組成物
PT103661B (pt) Processo de preparação de minociclina base cristalina
EP1737828A1 (fr) Sels de magnesium amorphes de la rosuvastatine
CN1180359A (zh) 子囊霉素
JP2008524125A (ja) 臭化水素酸ガランタミンの製造方法
TWI585092B (zh) 晶狀（１ｒ，４ｒ）－６’－氟基－Ｎ，Ｎ－二甲基－４－苯基－４’，９’－二氫－３’Ｈ－螺［環己烷－１，１’－吡喃［３，４，ｂ］吲哚］－４－胺
WO2005066196A1 (fr) Forme amorphe de finasteride et procede de preparation associe
CA2519752A1 (fr) Procede de preparation de ciclesonide cristallin de granulometrie definie
WO2005123721A2 (fr) Formes amorphes et polymorphes de candesartan cilexetil
US11466049B2 (en) Method for purifying crude rocuronium bromide
EP1633364B1 (fr) Procedes de fabrication de sildenafil base et de son sel citrate
JP6952206B2 (ja) メサコニンおよびその関連中間体の製造方法
WO2004087660A1 (fr) Nouveau procede de preparation d'une forme amorphe de chlorhydrate de donepezil
EA015727B1 (ru) Способ получения кандесартана цилексетила
WO2005092886A1 (fr) Procede de preparation d'une forme amorphe de la tiagabine
US7393964B2 (en) Process for the preparation of norelgestromin
CN115197119B (zh) 一种6,6-二甲基-3-氮杂双环[3.1.0]己烷-2,4-二酮的制备方法
PL209409B1 (pl) Polimorficzna forma B estru dodekahydrocyklopenta(a)fenantrylowego kwasu tiofenokarboksylowego, kompozycja farmaceutyczna zawierająca tę formę polimorficzną, zastosowanie tej formy polimorficznej oraz sposób jej wytwarzania
WO2004099142A1 (fr) Sel de bromhydrate de benzyl-piperidylmethyl-indanone et ses polymorphes
JP2013227273A (ja) ４′−［［２−ｎ−プロピル−４−メチル−６−（１−メチルベンズイミダゾール−２−イル）−ベンズイミダゾール−１−イル］−メチル］−ビフェニル−２−カルボン酸の精製方法
WO2004039352A2 (fr) Forme amorphe de losartan potassium
JP2009533432A (ja) ナルコチンの精製方法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: DE

WWW Wipo information: withdrawn in national office

Country of ref document: DE

122 Ep: pct application non-entry in european phase