WO1999032484A1 - Process for the preparation of paroxetine hydrochloride - Google Patents
Process for the preparation of paroxetine hydrochloride Download PDFInfo
- Publication number
- WO1999032484A1 WO1999032484A1 PCT/GB1998/003836 GB9803836W WO9932484A1 WO 1999032484 A1 WO1999032484 A1 WO 1999032484A1 GB 9803836 W GB9803836 W GB 9803836W WO 9932484 A1 WO9932484 A1 WO 9932484A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- paroxetine hydrochloride
- propan
- solvate
- preparation
- disorders
- 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
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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
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
Definitions
- the present invention relates to a process for the preparation of a pharmaceutically active compound, and to the use of the so-prepared compound in therapy.
- this invention is concerned with a new process for the preparation of a paroxetine chloride propan-2-ol solvate and its use to prepare a crystalline anhydrate form of paroxetine hydrochloride.
- 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 WO96/24595 of SmithKline Beecham).
- WO96/24595 describes the preparation of the form A anhydrate via an intermediate solvate with an organic solvent such as propan-2-ol.
- paroxetine hydrochloride propan-2-ol solvate When prepared conventionally (crystallisation from anhydrous propan-2-ol), paroxetine hydrochloride propan-2-ol solvate has very poor stirring properties, and is very difficult to isolate, wash, and dry. It is also very difficult to desolvate by heat treatment under vacuum. In WO96/24595, the problem that conventional drying techniques were incapable of efficient removal of solvent was addressed by providing an additional displacement stage before the product was finally dried.
- the present invention is based on the finding that crystallisation of paroxetine hydrochloride from a mixture of propan-2-ol and a co-solvent produces an improved crystalline form which is much easier to stir, filter, wash and dry. Surprisingly it has also been found that it is easier to remove solvent of crystallisation by heat treatment.
- the present invention provides a process for the preparation of paroxetine hydrochloride propan-2-ol solvate which comprises forming a solution of paroxetine hydrochloride in a mixture of propan-2-ol and an effective co-solvent, and crystallising paroxetine hydrochloride propan-2-ol solvate from the solution.
- an effective cosolvent is one which will form a clear solution when added to a solution of paroxetine hydrochloride in propan-2-ol and which does not form a competing solvate during crystallisation.
- Suitable cosolvents include toluene, heptane and hexane. Surprisingly toluene has been found to be particularly useful despite the fact that a toluene solvate of paroxetine hydrochloride can exist.
- the cosolvent mixture may formed before addition of paroxetine hydrochloride, or by addition of a cosolvent to a solution of paroxetine hydrochloride in propan-2-ol, or by addition of propan-2-ol to a solution of paroxetine hydrochloride in an effective cosolvent.
- the final stage of the preparation of paroxetine hydrochloride is carried out in an effective cosolvent, to which propan-2-ol may be added for crystallisation in accordance with the invention.
- toluene is used as the cosolvent it can be used conveniently in the preceding manufacturing step. After washing and acidification, only partial evaporation is necessary, followed by addition of propan-2-ol and crystallisation.
- Crystallisation may be initiated by conventional procedures such as cooling a heated solution, or removing solvent by evaporation or heating. It may be advantageous to add seeds of crystalline paroxetine hydrochloride propan-2-ol solvate prepared by the procedure of this invention or by the procedure of WO96/24595.
- a crystalline anhydrate of paroxetine hydrochloride may be formed by heating the propan-2-ol solvate to remove bound propan-2-ol.
- the resultant product desirably contains less than 2% of the solvated solvent, preferably less than 1%, more preferably less than 0.5%o, and most preferably less than 0.1%>.
- the crystalline product is the Form A anhydrate of paroxetine hydrochloride.
- the crystalline paroxetine hydrochloride product of this invention may be formulated for therapy as described in EP-A-0223403 or WO96/00477.
- 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, premenstrual 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, premenstrual syndrome (PMS), adolescent depression, trichotillomania, dysthymia, and substance abuse, referred to below as "the disorders”.
- the present invention also provides: a pharmaceutical composition for treatment or prophylaxis of the disorders comprising paroxetine hydrochloride anhydrate prepared by this invention and a pharmaceutically acceptable carrier;
- paroxetine hydrochloride anhydrate 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 which comprises administering an effective or prophylactic amount of paroxetine hydrochloride anhydrate prepared by this invention to a person suffering from one or more of the disorders.
- Paroxetine hydrochloride hemihydrate 160 g was suspended in a mixture of toluene (250 mil) and isopropanol (1000 ml) and heated to boiling. Solvent was removed by distillation and replaced by fresh isopropanol (3 x 500 ml). The boiling point was then 81.2°C. Further solvent was removed by distillation until the volume was about 1000 ml. The well stirred mixture was allowed to cool to about 70°C, then hexane (500 ml) was added slowly to give a clear solution at 57°C. Seeds of paroxetine hydrochloride isopropanol solvate were added, and as the crystallisation proceeded the temperature increased to 60°C. Stirring was continued until the temperature had fallen to about 30°C, then the product was collected, washed on the filter with hexane (2 x 500 ml) and dried in vacuo at ambient temperature.
- Paroxetine hydrochloride hemihydrate (122 g) was suspended in toluene (1000 ml) and heated to reflux for 2 hours under Dean & Stark apparatus to remove water. The toluene solution was concentrated to approximately 250 ml volume at which point it was still mobile and easy to stir. Warm propan-2-ol was added (1300 ml at about 50°C) and the reaction mixture stirred vigorously; the mixture crystallised slowly but did not become unstirrable.
- paroxetine hydrochloride containing approximately 1.6% propan-2-ol.
- a conventionally prepared sample of solvate heated overnight in a vacuum oven at 70°C for 24 hours contained 4.1% propan-2-ol.
- Paroxetine hydrochloride hemihydrate 50 g was heated to reflux with stirring in toluene (500 ml) and the water removed using a Dean and Stark apparatus. The solution was allowed to cool to about 40°C, diluted with isopropanol (200 ml), and allowed to crystallize at ambient temperature. The product was collected, washed with toluene and dried at 40°C to give paroxetine hydrochloride isopropanol solvate.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
A process for the preparation of paroxetine hydrochloride propan-2-ol solvate comprises forming a solution of paroxetine hydrochloride in a mixture of propan-2-ol and an effective co-solvent, and crystallising paroxetine hydrochloride propan-2-ol solvate from the solution.
Description
PROCESS FOR THE PREPARATION OF PAROXETINE HYDROCHLORIDE
The present invention relates to a process for the preparation of a pharmaceutically active compound, and to the use of the so-prepared compound in therapy. In particular this invention is concerned with a new process for the preparation of a paroxetine chloride propan-2-ol solvate and its use to prepare a crystalline anhydrate form of paroxetine hydrochloride.
Pharmaceutical products with antidepressant and anti-Parkinson properties are described in US-A-3912743 and US-A-4007196. An especially important compound among those disclosed is paroxetine, the (-)trans isomer of 4-(4'-fluorophenyl)-3- (3',4'-methylenedioxy-phenoxymethyl)-piperidine. This compound is used in therapy as the hydrochloride salt for the treatment and prophylaxis of ter alia depression, obsessive compulsive disorder (OCD) and panic.
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 WO96/24595 of SmithKline Beecham). WO96/24595 describes the preparation of the form A anhydrate via an intermediate solvate with an organic solvent such as propan-2-ol.
When prepared conventionally (crystallisation from anhydrous propan-2-ol), paroxetine hydrochloride propan-2-ol solvate has very poor stirring properties, and is very difficult to isolate, wash, and dry. It is also very difficult to desolvate by heat treatment under vacuum. In WO96/24595, the problem that conventional drying techniques were incapable of efficient removal of solvent was addressed by providing an additional displacement stage before the product was finally dried.
The present invention is based on the finding that crystallisation of paroxetine hydrochloride from a mixture of propan-2-ol and a co-solvent produces an improved crystalline form which is much easier to stir, filter, wash and dry. Surprisingly it has also been found that it is easier to remove solvent of crystallisation by heat treatment.
Accordingly the present invention provides a process for the preparation of paroxetine hydrochloride propan-2-ol solvate which comprises forming a solution of paroxetine hydrochloride in a mixture of propan-2-ol and an effective co-solvent, and crystallising paroxetine hydrochloride propan-2-ol solvate from the solution.
Typically an effective cosolvent is one which will form a clear solution when added to a solution of paroxetine hydrochloride in propan-2-ol and which does not form a competing solvate during crystallisation. Suitable cosolvents include toluene, heptane and hexane. Surprisingly toluene has been found to be particularly useful despite the fact that a toluene solvate of paroxetine hydrochloride can exist.
The cosolvent mixture may formed before addition of paroxetine hydrochloride, or by addition of a cosolvent to a solution of paroxetine hydrochloride in propan-2-ol, or by addition of propan-2-ol to a solution of paroxetine hydrochloride in an effective cosolvent. In a preferred procedure, the final stage of the preparation of paroxetine hydrochloride is carried out in an effective cosolvent, to which propan-2-ol may be added for crystallisation in accordance with the invention. For example when toluene is used as the cosolvent it can be used conveniently in the preceding manufacturing step. After washing and acidification, only partial evaporation is necessary, followed by addition of propan-2-ol and crystallisation.
Crystallisation may be initiated by conventional procedures such as cooling a heated solution, or removing solvent by evaporation or heating. It may be advantageous to add seeds of crystalline paroxetine hydrochloride propan-2-ol solvate prepared by the procedure of this invention or by the procedure of WO96/24595.
A crystalline anhydrate of paroxetine hydrochloride may be formed by heating the propan-2-ol solvate to remove bound propan-2-ol. The resultant product desirably contains less than 2% of the solvated solvent, preferably less than 1%, more preferably less than 0.5%o, and most preferably less than 0.1%>. Advantageously the crystalline product is the Form A anhydrate of paroxetine hydrochloride.
The crystalline paroxetine hydrochloride product of this invention may be formulated for therapy as described in EP-A-0223403 or WO96/00477.
Therapeutic uses of the paroxetine product of this invention include treatment of: alcoholism, anxiety, depression, obsessive compulsive disorder, panic disorder, chronic pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia, premenstrual syndrome (PMS), adolescent depression, trichotillomania, dysthymia, and substance abuse, referred to below as "the disorders".
Accordingly, the present invention also provides:
a pharmaceutical composition for treatment or prophylaxis of the disorders comprising paroxetine hydrochloride anhydrate prepared by this invention and a pharmaceutically acceptable carrier;
the use of paroxetine hydrochloride anhydrate prepared by the process of this invention to manufacture a medicament for the treatment or prophylaxis of the disorders; and
a method of treating the disorders which comprises administering an effective or prophylactic amount of paroxetine hydrochloride anhydrate prepared by this invention to a person suffering from one or more of the disorders.
The invention is illustrated by the following Examples:
Example 1
Paroxetine hydrochloride hemihydrate (160 g) was suspended in a mixture of toluene (250 mil) and isopropanol (1000 ml) and heated to boiling. Solvent was removed by distillation and replaced by fresh isopropanol (3 x 500 ml). The boiling point was then 81.2°C. Further solvent was removed by distillation until the volume was about 1000 ml. The well stirred mixture was allowed to cool to about 70°C, then hexane (500 ml) was added slowly to give a clear solution at 57°C. Seeds of paroxetine hydrochloride isopropanol solvate were added, and as the crystallisation proceeded the temperature increased to 60°C. Stirring was continued until the temperature had fallen to about 30°C, then the product was collected, washed on the filter with hexane (2 x 500 ml) and dried in vacuo at ambient temperature.
Yield 171 g isopropanol content by NMR: 10.5% wt wt
Example 2
(-)-Trans-4-(4-fluorophenyl)-3-(3',4'-methylenedioxyphenoxymethyl)-l- phenoxycarbonylpiperidine (90 g) is heated with potassium hydroxide (8.5 g) in toluene (1500 ml) at reflux for 3 hours, cooled, washed with hot water, acidified with hydrochloric acid, and distilled to approximately one quarter volume under vacuum. Hot propan-2-ol (2000 ml) is added and the mixture cooled slowly with vigorous stirring until the temperature reaches 20°C. After stirring for a further 2 hours, the
product is filtered, washed with propan-2-ol, and dried under vacuum, to give paroxetine hydrochloride propan-2-ol solvate.
Example 3
Paroxetine hydrochloride hemihydrate (122 g) was suspended in toluene (1000 ml) and heated to reflux for 2 hours under Dean & Stark apparatus to remove water. The toluene solution was concentrated to approximately 250 ml volume at which point it was still mobile and easy to stir. Warm propan-2-ol was added (1300 ml at about 50°C) and the reaction mixture stirred vigorously; the mixture crystallised slowly but did not become unstirrable. After about 30 minutes a further quantity of propan-2-ol (300 ml) and n-heptane (300 ml) was added, and the mixture was cooled to ambient temperature (approximately 20°C), stirred for a further 30 minutes, filtered and dried.
One part of the product was dried under vacuum at approximately 20°C to give paroxetine hydrochloride propan-2-ol solvate with a composition ratio of approximately 1 :1.
Another part was dried under vacuum at a final temperature of 65°C to give paroxetine hydrochloride containing approximately 1.6% propan-2-ol. By comparison, a conventionally prepared sample of solvate heated overnight in a vacuum oven at 70°C for 24 hours contained 4.1% propan-2-ol.
Example 4
Paroxetine hydrochloride hemihydrate (50 g) was heated to reflux with stirring in toluene (500 ml) and the water removed using a Dean and Stark apparatus. The solution was allowed to cool to about 40°C, diluted with isopropanol (200 ml), and allowed to crystallize at ambient temperature. The product was collected, washed with toluene and dried at 40°C to give paroxetine hydrochloride isopropanol solvate.
Yield 23 g
Claims
1. A process for the preparation of paroxetine hydrochloride propan-2-ol solvate which comprises forming a solution of paroxetine hydrochloride in a mixture of propan-2-ol and an effective co-solvent, and crystallising paroxetine hydrochloride propan-2-ol solvate from the solution.
2. A process according to claim 1 wherein the cosolvent comprises toluene, heptane or hexane.
3. A process according to claim 1 or 2 wherein the final stage of the preparation of paroxetine hydrochloride is carried out in the cosolvent, to which propan-2-ol is subsequently added for crystallisation.
4. A process for the preparation of a crystalline anhydrate of paroxetine hydrochloride which comprises heating a propan-2-ol solvate , obtained using the process of any one of the preceding claims, to remove bound propan-2-ol.
5. A pharmaceutical composition for treatment or prophylaxis of the disorders comprising paroxetine hydrochloride anhydrate prepared by the process of claim 4 and a pharmaceutically acceptable carrier.
6. The use of paroxetine hydrochloride anhydrate prepared by the process of claim 4 to manufacture a medicament for the treatment or prophylaxis of the disorders.
7. A method of treating the disorders which comprises administering an effective or prophylactic amount of paroxetine hydrochloride anhydrate prepared by the process of claim 4 to a person suffering from one or more of the disorders.
Priority Applications (14)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU17698/99A AU1769899A (en) | 1997-12-19 | 1998-12-18 | Process for the preparation of paroxetine hydrochloride |
| APAP/P/2000/001836A AP2000001836A0 (en) | 1997-12-19 | 1998-12-18 | Process for the preparation of paroxetine hydrochloride. |
| CA002315066A CA2315066A1 (en) | 1997-12-19 | 1998-12-18 | Process for the preparation of paroxetine hydrochloride |
| KR1020007006764A KR20010033317A (en) | 1997-12-19 | 1998-12-18 | Process for the Preparation of Paroxetine Hydrochloride |
| EP98962563A EP1042318A1 (en) | 1997-12-19 | 1998-12-18 | Process for the preparation of paroxetine hydrochloride |
| HU0004503A HUP0004503A3 (en) | 1997-12-19 | 1998-12-18 | Process for the preparation of paroxetine hydrochloride |
| SK924-2000A SK9242000A3 (en) | 1997-12-19 | 1998-12-18 | Process for the preparation of paroxetine hydrochloride |
| BR9813638-0A BR9813638A (en) | 1997-12-19 | 1998-12-18 | "process for the preparation of paroxetine hydrochloride" |
| JP2000525421A JP2001526288A (en) | 1997-12-19 | 1998-12-18 | Preparation of paroxetine hydrochloride |
| EA200000689A EA200000689A1 (en) | 1997-12-19 | 1998-12-18 | METHOD OF OBTAINING PAROXETHINE HYDROCHLORIDE |
| IL13659098A IL136590A0 (en) | 1997-12-19 | 1998-12-18 | Process for preparation of paroxetine hydrochloride |
| PL98341358A PL341358A1 (en) | 1997-12-19 | 1998-12-18 | Method of obtaining paroxetin chlorhydride |
| NO20003145A NO20003145L (en) | 1997-12-19 | 2000-06-16 | Process for the preparation of paroxetine hydrochloride |
| BG104604A BG104604A (en) | 1997-12-19 | 2000-07-13 | Process for the preparation of paroxetin hydrochloride |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9726907.0 | 1997-12-19 | ||
| GBGB9726907.0A GB9726907D0 (en) | 1997-12-19 | 1997-12-19 | Novel compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1999032484A1 true WO1999032484A1 (en) | 1999-07-01 |
Family
ID=10823933
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1998/003836 Ceased WO1999032484A1 (en) | 1997-12-19 | 1998-12-18 | Process for the preparation of paroxetine hydrochloride |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP1042318A1 (en) |
| JP (1) | JP2001526288A (en) |
| KR (1) | KR20010033317A (en) |
| CN (1) | CN1281448A (en) |
| AP (1) | AP2000001836A0 (en) |
| AU (1) | AU1769899A (en) |
| BG (1) | BG104604A (en) |
| BR (1) | BR9813638A (en) |
| CA (1) | CA2315066A1 (en) |
| EA (1) | EA200000689A1 (en) |
| GB (1) | GB9726907D0 (en) |
| HU (1) | HUP0004503A3 (en) |
| ID (1) | ID24733A (en) |
| IL (1) | IL136590A0 (en) |
| NO (1) | NO20003145L (en) |
| OA (1) | OA11635A (en) |
| PL (1) | PL341358A1 (en) |
| SK (1) | SK9242000A3 (en) |
| TR (1) | TR200001933T2 (en) |
| WO (1) | WO1999032484A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001012623A1 (en) * | 1999-08-12 | 2001-02-22 | Smithkline Beecham P.L.C. | Process for the preparation of paroxetine hydrochloride |
| WO2001025232A1 (en) * | 1999-10-04 | 2001-04-12 | Smithkline Beecham Plc | Process for the preparation of paroxetine hydrochloride acetone solvate |
| US6686473B2 (en) | 2001-02-21 | 2004-02-03 | Synthon Bct Technologies, Llc | Process for the production of paroxetine |
| EP1482939A4 (en) * | 2002-02-22 | 2005-10-12 | Teva Pharma | Preparation of paroxetine involving novel intermediates |
| US7229980B2 (en) | 2004-09-21 | 2007-06-12 | Chong Kun Dang Pharmaceutical Corp. | Paroxetine cholate or cholic acid derivative salts, and composition comprising paroxetine and cholic acid or derivative thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0223403A2 (en) * | 1985-10-25 | 1987-05-27 | Beecham Group Plc | Piperidine derivative, its preparation, and its use as medicament |
| WO1996024595A1 (en) * | 1995-02-06 | 1996-08-15 | Smithkline Beecham Plc | New forms of paroxetin hydrochloride |
| CA2187128A1 (en) * | 1996-10-04 | 1997-06-26 | K. S. Keshava Murthy | New and useful polymorph of anhydrous paroxetine hydrochloride |
-
1997
- 1997-12-19 GB GBGB9726907.0A patent/GB9726907D0/en not_active Ceased
-
1998
- 1998-12-18 AP APAP/P/2000/001836A patent/AP2000001836A0/en unknown
- 1998-12-18 EP EP98962563A patent/EP1042318A1/en not_active Withdrawn
- 1998-12-18 BR BR9813638-0A patent/BR9813638A/en not_active Application Discontinuation
- 1998-12-18 AU AU17698/99A patent/AU1769899A/en not_active Abandoned
- 1998-12-18 HU HU0004503A patent/HUP0004503A3/en unknown
- 1998-12-18 CN CN98811920A patent/CN1281448A/en active Pending
- 1998-12-18 JP JP2000525421A patent/JP2001526288A/en active Pending
- 1998-12-18 WO PCT/GB1998/003836 patent/WO1999032484A1/en not_active Ceased
- 1998-12-18 SK SK924-2000A patent/SK9242000A3/en unknown
- 1998-12-18 CA CA002315066A patent/CA2315066A1/en not_active Abandoned
- 1998-12-18 KR KR1020007006764A patent/KR20010033317A/en not_active Withdrawn
- 1998-12-18 OA OA1200000182A patent/OA11635A/en unknown
- 1998-12-18 ID IDW20001158A patent/ID24733A/en unknown
- 1998-12-18 TR TR2000/01933T patent/TR200001933T2/en unknown
- 1998-12-18 IL IL13659098A patent/IL136590A0/en unknown
- 1998-12-18 PL PL98341358A patent/PL341358A1/en unknown
- 1998-12-18 EA EA200000689A patent/EA200000689A1/en unknown
-
2000
- 2000-06-16 NO NO20003145A patent/NO20003145L/en not_active Application Discontinuation
- 2000-07-13 BG BG104604A patent/BG104604A/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0223403A2 (en) * | 1985-10-25 | 1987-05-27 | Beecham Group Plc | Piperidine derivative, its preparation, and its use as medicament |
| WO1996024595A1 (en) * | 1995-02-06 | 1996-08-15 | Smithkline Beecham Plc | New forms of paroxetin hydrochloride |
| CA2187128A1 (en) * | 1996-10-04 | 1997-06-26 | K. S. Keshava Murthy | New and useful polymorph of anhydrous paroxetine hydrochloride |
Non-Patent Citations (2)
| Title |
|---|
| BUXTON P C ET AL: "SOLID-STATE FORMS OF PAROXETINE HYDROCHLORIDE", INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 42, 1 January 1988 (1988-01-01), pages 135 - 143, XP000572028 * |
| LYNCH, IAN R. ET AL: "Infrared spectroscopic studies on the solid state forms of paroxetine hydrochloride", ANAL. PROC. (LONDON) (1988), 25(9), 305-6 CODEN: ANPRDI;ISSN: 0144-557X, XP000572171 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001012623A1 (en) * | 1999-08-12 | 2001-02-22 | Smithkline Beecham P.L.C. | Process for the preparation of paroxetine hydrochloride |
| WO2001025232A1 (en) * | 1999-10-04 | 2001-04-12 | Smithkline Beecham Plc | Process for the preparation of paroxetine hydrochloride acetone solvate |
| US6686473B2 (en) | 2001-02-21 | 2004-02-03 | Synthon Bct Technologies, Llc | Process for the production of paroxetine |
| EP1482939A4 (en) * | 2002-02-22 | 2005-10-12 | Teva Pharma | Preparation of paroxetine involving novel intermediates |
| US7229980B2 (en) | 2004-09-21 | 2007-06-12 | Chong Kun Dang Pharmaceutical Corp. | Paroxetine cholate or cholic acid derivative salts, and composition comprising paroxetine and cholic acid or derivative thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| BG104604A (en) | 2001-03-30 |
| EP1042318A1 (en) | 2000-10-11 |
| BR9813638A (en) | 2000-10-17 |
| EA200000689A1 (en) | 2000-12-25 |
| GB9726907D0 (en) | 1998-02-18 |
| ID24733A (en) | 2000-08-03 |
| JP2001526288A (en) | 2001-12-18 |
| TR200001933T2 (en) | 2000-12-21 |
| SK9242000A3 (en) | 2001-01-18 |
| CN1281448A (en) | 2001-01-24 |
| HUP0004503A2 (en) | 2002-03-28 |
| AP2000001836A0 (en) | 2000-06-30 |
| NO20003145D0 (en) | 2000-06-16 |
| AU1769899A (en) | 1999-07-12 |
| KR20010033317A (en) | 2001-04-25 |
| OA11635A (en) | 2004-11-22 |
| IL136590A0 (en) | 2001-06-14 |
| HUP0004503A3 (en) | 2002-04-29 |
| PL341358A1 (en) | 2001-04-09 |
| CA2315066A1 (en) | 1999-07-01 |
| NO20003145L (en) | 2000-06-16 |
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