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WO2000032593A1 - Procede de fabrication d'hydrochlorure de paroxetine - Google Patents

Procede de fabrication d'hydrochlorure de paroxetine Download PDF

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Publication number
WO2000032593A1
WO2000032593A1 PCT/GB1999/003992 GB9903992W WO0032593A1 WO 2000032593 A1 WO2000032593 A1 WO 2000032593A1 GB 9903992 W GB9903992 W GB 9903992W WO 0032593 A1 WO0032593 A1 WO 0032593A1
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WO
WIPO (PCT)
Prior art keywords
hydrochloride
paroxetine
amine
isolated
process according
Prior art date
Application number
PCT/GB1999/003992
Other languages
English (en)
Inventor
Andrew Simon Craig
David Alan Jones
Original Assignee
Smithkline Beecham Plc
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 Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Priority to EP99973026A priority Critical patent/EP1135382A1/fr
Priority to JP2000585235A priority patent/JP2002531451A/ja
Priority to AU13978/00A priority patent/AU1397800A/en
Publication of WO2000032593A1 publication Critical patent/WO2000032593A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32—Alcohol-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • This invention is concerned with a new process for the preparation of hydrochloride salts of paroxetine.
  • Paroxetine hydrochloride has been described in the literature as a crystalline hemihydrate (see EP-A-0223403 of Beecham Group) and as various crystalline anhydrate forms (see WO 96/24595 of SmithKline Beecham pic).
  • This invention aims to overcome disadvantages in the existing processes for preparation of paroxetine hydrochloride and so to provide alternative processes for its manufacture.
  • paroxetine hydrochloride is usually prepared by acidification of a solution of paroxetine base obtained as the final stage of a synthetic sequence.
  • the preparation of paroxetine hydrochloride by addition of aqueous hydrochloric acid requires very acidic conditions for the formation of the salt from paroxetine base and this can result in the formation of unwanted impurities.
  • the alternative use of hydrogen chloride gas on a large scale gives rise to high capital equipment costs and dangers of gas handling.
  • the preparation of hydrogen chloride solutions in some solvents, for example ketones such as acetone and butanone results in undesirable reactions, such as aldol condensation.
  • WO 98/01424 (Richter Gedeon) describes procedures in which solutions of paroxetine acetate and tartrate salts are treated with aqueous solutions of sodium chloride or ammonium chloride to form paroxetine hydrochloride hemihydrate.
  • paroxetine hydrochloride can be prepared directly from paroxetine free base without the need for an intermediate salt, which is suitable for use under anhydrous conditions as well as aqueous conditions, and which is therefore suitable for the manufacture of anhydrous and solvated forms of paroxetine.
  • the present invention provides a process for the preparation of paroxetine hydrochloride in which a solution of paroxetine base or a salt other than the hydrochloride is contacted with an amine hydrochloride, and paroxetine hydrochloride is isolated as a solid, with the proviso that the use of ammonium chloride is excluded when treating paroxetine acetate or paroxetine tartrate in an aqueous system to obtain paroxetine hydrochloride for isolation as the hemihydrate.
  • the present invention provides a process for the preparation of paroxetine hydrochloride anhydrate or solvate in which a solution of paroxetine base or a salt other than the hydrochloride is contacted with an amine hydrochloride, and paroxetine hydrochloride is isolated as an anhydrate or solvate, preferably in crystalline form.
  • the present invention provides a process for the preparation of non- crystalline paroxetine hydrochloride in which a solution of paroxetine base or a salt other than the hydrochloride is contacted with an amine hydrochloride, and paroxetine hydrochloride is isolated in non-crystalline form.
  • the present invention provides a process for the preparation of paroxetine hydrochloride hemihydrate in which a solution of paroxetine base is contacted with an amine hydrochloride in the presence of water, and paroxetine hydrochloride is isolated as the crystalline hemihydrate.
  • the present invention provides a process for the preparation of a paroxetine hydrochloride hemihydrate in which a solution of a paroxetine salt other than the hydrochloride, is contacted with an amine hydrochloride other than ammonium chloride in the presence of water, and paroxetine hydrochloride is isolated as the crystalline hemihydrate.
  • the present invention provides a process for the preparation of a paroxetine hydrochloride hemihydrate in which a solution of a paroxetine salt other than the hydrochloride, acetate, or tartrate is contacted with ammonium chloride in the presence of water, and paroxetine hydrochloride is isolated as the crystalline hemihydrate.
  • This invention allows for the use of a mild, convenient, solid, cheap source of hydrogen chloride that can be conveniently added without expensive toxic gas handling facilities under mild conditions.
  • the process can also be easily made anhydrous for the preparation of anhydrous forms of paroxetine hydrochloride; ambient temperature may be used and rigorous removal of water and complex solvent handling procedures are rendered unnecessary.
  • the formation of paroxetine hydrochloride/amine hydrochloride crystalline 1:1 complexes is avoided by control of seeding or by avoiding excessively high concentrations.
  • the treatment with the amine hydrochloride preferably takes place under an atmosphere of inert gas, such as nitrogen or argon.
  • the paroxetine hydrochloride may be isolated in non- crystalline form, for example by spray-drying or tray-drying, or as crystalline forms such as the hemihydrate, by crystallising from water or water-containing solutions, or as a crystalline anhydrate, or a crystalline solvate, such as the propan-2-ol, acetone, or toluene solvate, by crystallising from anhydrous solutions.
  • the amine hydrochloride is most conveniently commercially available material that can be used as supplied, but it may also be prepared in situ, for example by reaction of an amine with hydrogen chloride gas in a solvent.
  • the amine hydrochloride may be used as a solid or in solution, and is preferably of low molecular weight.
  • Suitable amine hydrochlorides are ammonium chloride, or based on primary alkylamines, preferably C,.
  • alkyl for example methylamine hydrochloride or ethylamine hydrochloride; primary aralkylamine, for example aryl C M alkyl such as benzylamine hydrochloride; secondary alkylamine, preferably di-C alkyl for example dimethylamine hydrochloride or diethylamine hydrochloride; aromatic amine hydrochlorides, for example aniline hydrochloride; or heteroaromatic hydrochlorides, for example pyridine hydrochloride or collidine hydrochloride.
  • high molecular weight polymeric amine hydrochlorides may be used, for example polyvinylpyridine hydrochloride. It may be convenient to use a highly volatile amine salt such as methylamine hydrochloride, since purging the reaction mixture with an inert gas causes the free amine to be removed.
  • the isolation process may be by crystallisation and may include a conjugate amine removal step, for example by purging, filtering, or washing and drying.
  • a non-crystalline solid product may be isolated by spray drying, in which case it is particularly advantageous to use a highly volatile amine.
  • an anhydrous solvent is used for the preparation of anhydrous forms of paroxetine hydrochloride, and water or a water-containing solvent mixture is used to prepare paroxetine hydrochloride hemihydrate.
  • Suitable non-aqueous solvents include ethanol, propan-2-ol, butan-1-ol, toluene, acetone, ethyl acetate, and butanone.
  • Paroxetine base may be prepared in situ, for example by deprotection of (-)-trans-4-(4'- fluorophenyl)-3-(3'-4'-methylenedioxyphenoxymethyl-N-phenoxycarbonylpiperidine with potassium hydroxide in toluene followed by aqueous work up and phase separation.
  • the resulting solution of base is conveniently dried by partial azeotropic distillation of the solvent, or the solvent may be removed completely by distillation and replaced by another solvent.
  • the preparation of the base is described in Example 2 of US 4007196.
  • Suitable salts for starting materials include the maleic acid salt, also described in Example 2 of US 4007196.
  • the acetate salt may also be used as a starting material. Procedures for forming salts are described in EP-A-0223403.
  • Paroxetine hydrochloride products of this invention may be formulated for therapy as described in EP-A-0223403 or WO 96/00477.
  • the paroxetine hydrochloride is typically formulated with conventional excipients for tablet formation or with solid diluents for use as a powder fill for capsules.
  • the amount of paroxetine used is adjusted such that in a single unit dose there is a therapeutically effective amount of paroxetine.
  • the unit dose contains from 10 to 100 mg paroxetine (measured in terms of the base). More preferably the amount of paroxetine in a unit dose is lOmg, 20mg, 30mg, 40mg or 50mg. The most preferred amount of paroxetine in a unit dose is 20mg.
  • paroxetine product of this invention includes treatment of: alcoholism, anxiety, depression, obsessive compulsive disorder, panic disorder, chronic pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia, pre-menstrual syndrome (PMS), adolescent depression, trichotillomania, dysthymia, and substance abuse, referred to below as "the disorders”.
  • the disorders include treatment of: alcoholism, anxiety, depression, obsessive compulsive disorder, panic disorder, chronic pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia, pre-menstrual syndrome (PMS), adolescent depression, trichotillomania, dysthymia, and substance abuse, referred to below as "the disorders”.
  • the present invention also provides:
  • compositions for treatment or prophylaxis of the disorders comprising paroxetine hydrochloride prepared by this invention and a pharmaceutically acceptable carrier;
  • paroxetine hydrochloride prepared by the process of this invention to manufacture a medicament for the treatment or prophylaxis of the disorders
  • a method of treating the disorders that comprises administering an effective or prophylactic amount of paroxetine hydrochloride prepared by this invention to a person suffering from one or more of the disorders.
  • paroxetine base (5 g) in propan-2-ol (50 ml) was treated with one equivalent of pyridine hydrochloride at room temperature under argon. The resulting solution was stirred rapidly at room temperature whereupon crystallisation occurred. After 20 minutes stirring was stopped, and the suspension diluted with propan-2-ol and filtered. The solid product was dried in vacuo over phosphorous pentoxide to give paroxetine hydrochloride propan-2-ol solvate (4.83 g).
  • paroxetine hydrochloride base 8.7 g
  • toluene 200 ml
  • wet pyridine hydrochloride 3.0 g
  • the resulting solution was stirred rapidly at room temperature for 1 hour whereupon crystallisation occurred.
  • the solid was collected by filtration, washed with toluene, and dried in vacuo over phosphorous pentoxide to give paroxetine hydrochloride hemihydrate (4.69 g).
  • paroxetine base (5 g) in propan-2-oI (50 ml) was stirred with solid methylamine hydrochloride (1.0 g) at room temperature under nitrogen. The resulting solution was stirred rapidly at room temperature for 2 hours during which time a white precipitate formed. The precipitate was collected by filtration and dried in vacuo over phosphorous pentoxide to give paroxetine hydrochloride propan-2-ol solvate.
  • paroxetine base (5 g) in butan-1-ol (50 ml) was stirred with pyridine hydrochloride (1.76 g) at room temperature under nitrogen. The resulting solution was stirred rapidly for 1 hour while a white solid precipitated. The solid was collected by filtration and dried in vacuo over phosphorous pentoxide to give paroxetine hydrochloride anhydrate Form C (2.32 g).
  • paroxetine base (5 g) in propan-2-ol (50 ml) was stirred with ammonium chloride (1.0 g) at room temperature. A clear solution formed which was stirred rapidly at room temperature for 16 hours while a white crystalline solid precipitated. The solid was collected by filtration and dried in vacuo over phosphorous pentoxide to give paroxetine hydrochloride propan-2-ol solvate.
  • paroxetine base (5 g) in propan-2-ol (50 ml) was treated with polyvinylpyridine hydrochloride (2.3 g) at 50°C.
  • the reaction mixture was stirred for 30 minutes at the same temperature then filtered, and the filtrate cooled to room temperature.
  • This solution was seeded with paroxetine hydrochloride propan-2-ol solvate, and stirred vigorously at room temperature for 1 hour. Crystallisation ensued, and the solid was collected by filtration and dried in vacuo over phosphorous pentoxide to give paroxetine hydrochloride propan-2-ol solvate.
  • paroxetine base (4 g) in 2-butanone (40 ml) was treated with wet pyridine hydrochloride (1.40 g) at room temperature under argon. The resulting solution was stirred rapidly at room temperature for 16 hours while a white solid precipitated. This solid was collected by filtration, washed with butanone, and dried in vacuo over phosphorous pentoxide to give paroxetine hydrochloride hemihydrate (3.97 g).
  • paroxetine base (5 g) in propan-2-ol (50 ml) was treated with benzylamine hydrochloride (2.10 g) at room temperature under argon. The resulting solution was stirred rapidly at room temperature for 2.5 hours while a white precipitate formed. The resulting solid was collected by filtration, washed with propan-2-ol, and dried in vacuo over phosphorous pentoxide to give paroxetine hydrochloride propan-2-ol solvate (2.84 g).
  • paroxetine base in toluene (12 ml of a 0.42 g/ml solution) was diluted with propan-2-ol (40 ml), and aniline hydrochloride (1.96 g) was added with vigorous stirring.
  • the reaction mixture was stirred for 4 hours and the solid that crystallised was isolated by filtration, washed with propan-2-ol, and dried in vacuo over phosphorous pentoxide to give paroxetine hydrochloride propan-2-ol solvate (4.96 g).
  • Paroxetine free base (11.1 g) was dissolved in dry acetone (65 ml) under a nitrogen atmosphere and pyridine hydrochloride (4.1 g) added to the stirred solution. Crystallization started after less than one minute and proceeded to afford a thick suspension. The resulting paroxetine hydrochloride acetone solvate was collected by vacuum filtration, washed with acetone and dried at 60°C under vacuum for 20 hours.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biomedical Technology (AREA)
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  • Neurology (AREA)
  • Diabetes (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Addiction (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Emergency Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Rheumatology (AREA)
  • Hospice & Palliative Care (AREA)
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  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un nouveau procédé de préparation de composés actifs sur le plan pharmaceutique et d'intermédiaires de ces derniers. L'isomère trans (-) du 4-(4'-fluorophényl)-3-(3',4'-méthylènedioxyphénoxyméthyl)pipéridine (paroxétine) est un composé important qui présente des propriétés antidépressives et anti-Parkinson. Ce composé convient, comme le sel d'hydrochlorure, pour des thérapies visant à combattre, entre autres, la dépression, la psychonévrose obsessionnelle ou la panique. L'invention propose un procédé amélioré de préparation dudit composé, qui permet d'éviter la formation d'impuretés provoquées par les fortes concentrations d'acides minéraux nécessaires pour produire le sel.
PCT/GB1999/003992 1998-11-30 1999-11-30 Procede de fabrication d'hydrochlorure de paroxetine WO2000032593A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP99973026A EP1135382A1 (fr) 1998-11-30 1999-11-30 Procede de fabrication d'hydrochlorure de paroxetine
JP2000585235A JP2002531451A (ja) 1998-11-30 1999-11-30 パロキセチン塩酸塩の製法
AU13978/00A AU1397800A (en) 1998-11-30 1999-11-30 Method of producing paroxetine hydrochloride

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9826180.3 1998-11-30
GBGB9826180.3A GB9826180D0 (en) 1998-11-30 1998-11-30 Novel process

Publications (1)

Publication Number Publication Date
WO2000032593A1 true WO2000032593A1 (fr) 2000-06-08

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PCT/GB1999/003992 WO2000032593A1 (fr) 1998-11-30 1999-11-30 Procede de fabrication d'hydrochlorure de paroxetine

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EP (1) EP1135382A1 (fr)
JP (1) JP2002531451A (fr)
AU (1) AU1397800A (fr)
GB (1) GB9826180D0 (fr)
WO (1) WO2000032593A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001025231A1 (fr) * 1999-10-04 2001-04-12 Smithkline Beecham Plc Preparation d'un solvate cetonique de chlorhydrate de paroxetine
WO2002102382A1 (fr) * 2001-06-14 2002-12-27 Teva Pharmaceutical Industries Ltd. Procede de preparation de paroxetine hcl limitant la formation de composes colores en rose
WO2004026860A1 (fr) * 2002-09-19 2004-04-01 Sumitomo Chemical Company, Limited Procedes de precipitation cristalline
US7138137B2 (en) 2001-12-28 2006-11-21 Teva Pharmaceutical Industries Ltd. Stable pharmaceutical formulation of paroxetine hydrochloride and a process for preparation thereof
EP1726591A3 (fr) * 2005-05-26 2007-07-25 Apotecnia , S.A. Procedé de la Fabrication de l'Hemihydrate de l'Hydrochlorure de Paroxetine
EP1598346A4 (fr) * 2003-02-28 2007-08-15 Kowa Co Procede de production d'un sel d'addition d'acide d'un compose polyacide

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0223403A2 (fr) * 1985-10-25 1987-05-27 Beecham Group Plc Dérivé de pipéridine, sa préparation et son utilisation comme médicament
WO1996024595A1 (fr) * 1995-02-06 1996-08-15 Smithkline Beecham Plc Nouvelles formes de l'hydrochlorure de paroxetine
US5672612A (en) * 1996-09-09 1997-09-30 Pentech Pharmaceuticals, Inc. Amorphous paroxetine composition
EP0810224A1 (fr) * 1996-05-30 1997-12-03 Asahi Glass Company Ltd. Procédé de préparation de l'hydrochlorure de paroxétine amorphe
WO1998001424A1 (fr) * 1996-07-08 1998-01-15 Richter Gedeon Vegyészeti Gyár Rt. Derives de n-benzylpiperidine et de tetrahydropyridine

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0223403A2 (fr) * 1985-10-25 1987-05-27 Beecham Group Plc Dérivé de pipéridine, sa préparation et son utilisation comme médicament
WO1996024595A1 (fr) * 1995-02-06 1996-08-15 Smithkline Beecham Plc Nouvelles formes de l'hydrochlorure de paroxetine
EP0810224A1 (fr) * 1996-05-30 1997-12-03 Asahi Glass Company Ltd. Procédé de préparation de l'hydrochlorure de paroxétine amorphe
WO1998001424A1 (fr) * 1996-07-08 1998-01-15 Richter Gedeon Vegyészeti Gyár Rt. Derives de n-benzylpiperidine et de tetrahydropyridine
US5672612A (en) * 1996-09-09 1997-09-30 Pentech Pharmaceuticals, Inc. Amorphous paroxetine composition

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001025231A1 (fr) * 1999-10-04 2001-04-12 Smithkline Beecham Plc Preparation d'un solvate cetonique de chlorhydrate de paroxetine
WO2002102382A1 (fr) * 2001-06-14 2002-12-27 Teva Pharmaceutical Industries Ltd. Procede de preparation de paroxetine hcl limitant la formation de composes colores en rose
US7138137B2 (en) 2001-12-28 2006-11-21 Teva Pharmaceutical Industries Ltd. Stable pharmaceutical formulation of paroxetine hydrochloride and a process for preparation thereof
US7357945B2 (en) 2001-12-28 2008-04-15 Teva Pharmaceutical Industries Ltd. Stable pharmaceutical formulation of paroxetine hydrochloride and a process for preparation thereof
US7396542B2 (en) 2001-12-28 2008-07-08 Teva Pharmaceutical Industries Ltd. Stable pharmaceutical formulation of paroxetine hydrochloride anhydrous and a process for preparation thereof
WO2004026860A1 (fr) * 2002-09-19 2004-04-01 Sumitomo Chemical Company, Limited Procedes de precipitation cristalline
US7329318B2 (en) 2002-09-19 2008-02-12 Sumitomo Chemical Company, Limited Methods of crystal precipitation
AU2003271055B2 (en) * 2002-09-19 2009-03-12 Sumitomo Chemical Company, Limited Methods of crystal precipitation
EP1598346A4 (fr) * 2003-02-28 2007-08-15 Kowa Co Procede de production d'un sel d'addition d'acide d'un compose polyacide
US7750150B2 (en) 2003-02-28 2010-07-06 Kowa Co., Ltd. Process for producing acid adduct salt of polyacidic base compound
US8518936B2 (en) 2003-02-28 2013-08-27 Kowa Co., Ltd. Method for preparing acid addition salts of polyacidic basic compounds
EP1726591A3 (fr) * 2005-05-26 2007-07-25 Apotecnia , S.A. Procedé de la Fabrication de l'Hemihydrate de l'Hydrochlorure de Paroxetine

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JP2002531451A (ja) 2002-09-24
AU1397800A (en) 2000-06-19
EP1135382A1 (fr) 2001-09-26
GB9826180D0 (en) 1999-01-20

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