WO2001025232A1 - Process for the preparation of paroxetine hydrochloride acetone solvate - Google Patents

Process for the preparation of paroxetine hydrochloride acetone solvate Download PDF

Info

Publication number
WO2001025232A1
WO2001025232A1 PCT/GB2000/003802 GB0003802W WO0125232A1 WO 2001025232 A1 WO2001025232 A1 WO 2001025232A1 GB 0003802 W GB0003802 W GB 0003802W WO 0125232 A1 WO0125232 A1 WO 0125232A1
Authority
WO
WIPO (PCT)
Prior art keywords
paroxetine
paroxetine hydrochloride
acetone
solution
hydrochloric acid
Prior art date
Application number
PCT/GB2000/003802
Other languages
French (fr)
Inventor
Andrew Simon Craig
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 AU75428/00A priority Critical patent/AU7542800A/en
Publication of WO2001025232A1 publication Critical patent/WO2001025232A1/en

Links

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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • 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

Definitions

  • This invention relates to a process for the manufacture paroxetine hydrochloride acetone solvate, and in particular to a process which is suitable for large scale commercial operation.
  • Paroxetine hydrochloride has been described as a crystalline hemihydrate (see EP- 0223403) and as various crystalline anhydrate forms (see WO 96/24595).
  • a particularly useful crystalline form of paroxetine hydrochloride is paroxetine hydrochloride anhydrate Form A, which may be prepared by the desolvation of paroxetine hydrochloride solvates.
  • a particularly useful solvate for this purpose is paroxetine hydrochloride acetone solvate.
  • Example 9 of WO 96/24595 describes a laboratory scale preparation of paroxetine hydrochloride acetone solvate which involves the addition of a solution of hydrogen chloride in acetone to a solution of paroxetine free base in acetone. Although it is possible to carry out this procedure on a small scale by rapid addition of a freshly prepared solution of hydrogen chloride in acetone to a solution of paroxetine free base, this procedure is unsuitable for large scale manufacture due to the instability of the solution of hydrogen chloride in acetone.
  • Example 20 of WO 96/24595 describes the preparation of paroxetine hydrochloride acetone solvate by heating to reflux a suspension of paroxetine hydrochloride anhydrate Form C in acetone.
  • This method requires a large amount of solvent (15 volumes), which is an undesirable feature for a manufacturing process, but even at this dilution a clear solution is not obtained. Such a procedure therefore carries the risk of incomplete conversion, particularly on a large scale.
  • a procedure which requires paroxetine hydrochloride anhydrate Form C as a starting material involves an additional step in the reaction sequence, and adds to the cost and complexity of the operation.
  • This invention is based on the finding that the problems associated with the known process for preparing paroxetine hydrochloride acetone solvate may be overcome by selecting an alternative source of hydrogen chloride.
  • aqueous solvents is known to generate paroxetine hydrochloride hemihydrate
  • aqueous hydrochloric acid may be used as the source of hydrogen chloride, provided certain additional steps are employed.
  • aqueous hydrochloric acid as the source of hydrogen chloride in the process of this invention is particularly advantageous as aqueous hydrochloric acid is commercially available and inexpensive, and is stable and may be stored for extended periods of time.
  • Aqueous solutions may be used without the need for expensive specialised equipment such as that required to handle hydrogen chloride gas.
  • a solution of paroxetine base, or a salt of paroxetine with an organic acid, in an organic solvent is treated with aqueous hydrochloric acid.
  • the solution is then distilled to reduce the amount of water present and is then treated with acetone to afford paroxetine hydrochloride acetone solvate as a crystalline solid.
  • a suitable organic acid is acetic acid
  • Suitable solvents for the paroxetine free base or salt are acetone miscible solvents in which paroxetine free base and paroxetine hydrochloride are soluble.
  • Suitable solvents include: hydrocarbons for example toluene, xylene or heptane; esters for example ethylacetate or methylacetate; nitriles for example acetonitrile; ethers for example dioxane or tetrahydrofuran; halogenated hydrocarbons for example dichloromethane or chloroform and alcohols for example ethanol or propanol.
  • Preferred solvents are solvents which form an azeotrope with water and additionally do not form a solvate with paroxetine hydrochloride anhydrate Form A and hence do not compete with acetone as solvate molecules during the crystallization of paroxetme hydrochloride acetone solvate.
  • a particularly preferred solvent on a manufacturing scale is toluene, as a solution of paroxetine free base in toluene may be carried forward from a previous manufacturing step.
  • a particularly preferred source of source of hydrochloric acid on a manufacturing scale is concentrated hydrochloric acid as this minimises the amount of water to be removed by distillation. Addition of the aqueous hydrochloric acid may be carried out at ambient or elevated temperature.
  • paroxetine free base solution is treated with aqueous hydrochloric acid, then partial distillation is carried out in order to remove the water present as an azeotrope and the remaining solution is diluted with acetone to afford paroxetine hydrochloride acetone solvate as a crystalline solid.
  • the distillation of the paroxetine hydrochloride solution may be carried out at atmospheric, elevated or reduced pressure.
  • Treatment with acetone may be carried out at ambient, elevated or reduced temperature.
  • Paroxetme free base and salts may be prepared as described US 4,007, 196 or EP- 0,223,403.
  • paroxetine hydrochloride anhydrate Form A is manufactured by desolvating the acetone solvate by procedures described in WO 96/24595.
  • paroxetine hydrochloride anhydrate Form A obtainable by this mvention may be used in therapy in formulations described in EP-A-0223403 or WO 96/00477.
  • paroxetine hydrochloride anhydrate obtainable by this invention include treatment of inter alia : alcoholism, anxiety, depression, obsessive compulsive disorder (OCD), 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”.
  • OCD obsessive compulsive disorder
  • PMS pre-menstrual syndrome
  • adolescent depression trichotillomania
  • dysthymia substance abuse
  • the anhydrate obtainable by the present invention is applied to the treatment of depression, OCD and panic.
  • compositions prepared in accordance with this invention are usually adapted for oral administration, but formulations for dissolution for parental administration are also within the scope of this invention.
  • the composition is usually presented as a unit dose composition containing from 1 to 200mg of active ingredient calculated on a free base basis, more usually from 5 to 100 mg, for example 10 to 50 mg such as 10, 12.5, 15, 20, 25, 30 or 40 mg by a human patient. Most preferably unit doses contain 20 mg of active ingredient calculated on a free base basis. Such a composition is normally taken from 1 to 6 times daily, for example 2, 3 or 4 times daily so that the total amount of active agent administered is within the range 5 to 400 mg of active ingredient calculated on a free base basis. Most preferably the unit dose is taken once a day.
  • Preferred unit dosage forms include tablets or capsules, including formulations adapted for controlled or delayed release.
  • compositions of this invention may be formulated by conventional methods of admixture such as blending, filling and compressing.
  • Suitable carriers for use in this invention include a diluent, a binder, a disintegrant, a colouring agent, a flavouring agent and/or preservative. These agents may be utilized in conventional manner, for example in a manner similar to that already used for marketed anti-depressant agents.
  • compositions include those described EP-B- 0223403, and US 4,007,196 in which the anhydrate product of the present invention may be used as the active ingredient.
  • the present invention also provides: a pharmaceutical composition for treatment or prophylaxis of the Disorders comprising paroxetine hydrochloride anhydrate Form A obtainable by this invention and a pharmaceutically acceptable carrier;
  • paroxetine hydrochloride anhydrate Form A obtainable by 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 Form A obtainable by this invention to a person suffering from one or more of the Disorders.
  • IR (nujol mull) bands at cm" 1 3633, 3401, 1715, 1631, 1604, 1563, 1547, 1512, 1492, 1467, 1287, 1249, 1221, 1193, 1162, 1132, 1091, 1068, 1035, 1004, 968, 924, 908, 886, 831, 806, 783, 762, 721, 666, 614, 593, 572, 538.
  • the product was dried under vacuum at 60°C for 20 hours to give a product with an acetone content of 1.3 % by wt, as determined by 1H-NMR.
  • Example 2 A stirred mixture of N-phenoxycarbonyl paroxetine (19.4 g), potassium hydroxide (17.5 g) and toluene (300 ml) is heated to reflux under a nitrogen atmosphere for 3 hours. The mixture is cooled to room temperature, washed with water (200 ml) and the organic layer separated, dried over magnesium sulphate and concentrated to a total volume of 150 ml. Concentrated hydrochloric acid (3.5 ml) is added to the solution and the mixture stirred and heated to 75°C. The total volume of the reaction mixture is reduced to half by distillation under reduced pressure and dry acetone (75 ml) is added to the stirred reaction mixture, under a nitrogen atmosphere. The mixture is cooled to ambient temperature, stirred for 30 minutes and the product collected by filtration, washed with acetone (30 ml) and dried under vacuum at 60°C for 20 hours.
  • N-phenoxycarbonyl paroxetine (19.4 g)
  • potassium hydroxide 17.5 g

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

A process for preparing paroxetine hydrochloride acetone solvate, in which a solution of paroxetine base, or a salt of paroxetine with an organic acid, in an organic solvent is treated with aqueous hydrochloric acid, the solution is then distilled to reduce the amount of water present and is then treated with acetone to afford paroxetine hydrochloride acetone solvate as a crystalline solid.

Description

PROCESS FOR THE PREPARATION OF AROXETINE HYDROCHLORIDE ACETONE SOLVATE
This invention relates to a process for the manufacture paroxetine hydrochloride acetone solvate, and in particular to a process which is suitable for large scale commercial operation.
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',4'- methylenedioxy-phenoxymethyl)-piperidine. This compound is used in therapy as the hydrochloride salt to treat mter alia depression, obsessive compulsive disorder (OCD) and panic.
Paroxetine hydrochloride has been described as a crystalline hemihydrate (see EP- 0223403) and as various crystalline anhydrate forms (see WO 96/24595). A particularly useful crystalline form of paroxetine hydrochloride is paroxetine hydrochloride anhydrate Form A, which may be prepared by the desolvation of paroxetine hydrochloride solvates. A particularly useful solvate for this purpose is paroxetine hydrochloride acetone solvate.
Example 9 of WO 96/24595 describes a laboratory scale preparation of paroxetine hydrochloride acetone solvate which involves the addition of a solution of hydrogen chloride in acetone to a solution of paroxetine free base in acetone. Although it is possible to carry out this procedure on a small scale by rapid addition of a freshly prepared solution of hydrogen chloride in acetone to a solution of paroxetine free base, this procedure is unsuitable for large scale manufacture due to the instability of the solution of hydrogen chloride in acetone.
It is well documented that hydrogen chloride promotes aldol condensation reactions of ketones such as acetone, hence a solution of hydrogen chloride in acetone at ambient temperature will undergo self-condensation reactions and further reactions with the condensation products, leading to a cascade of side-reactions. Such a series of uncontrolled side reactions is a highly undesirable feature for a manufacturing process and can lead to non-reproducible reactions, and problems of contamination of the required product with impurities.
Water is generated as a side product of the aldol condensation reactions, the presence of which in the crystallization process has been found to lead to the formation of paroxetine hydrochloride hemihydrate.
There are further problems with the use of hydrogen chloride gas to prepare the solutions of hydrogen chloride in acetone on a manufacturing scale, for example the cost of the necessary capital equipment, the dangers of toxic gas handling, and the inability to store the solutions.
Example 20 of WO 96/24595 describes the preparation of paroxetine hydrochloride acetone solvate by heating to reflux a suspension of paroxetine hydrochloride anhydrate Form C in acetone. This method requires a large amount of solvent (15 volumes), which is an undesirable feature for a manufacturing process, but even at this dilution a clear solution is not obtained. Such a procedure therefore carries the risk of incomplete conversion, particularly on a large scale. Furthermore, a procedure which requires paroxetine hydrochloride anhydrate Form C as a starting material involves an additional step in the reaction sequence, and adds to the cost and complexity of the operation.
This invention is based on the finding that the problems associated with the known process for preparing paroxetine hydrochloride acetone solvate may be overcome by selecting an alternative source of hydrogen chloride. Although the use of aqueous solvents is known to generate paroxetine hydrochloride hemihydrate, we have surprisingly found that aqueous hydrochloric acid may be used as the source of hydrogen chloride, provided certain additional steps are employed.
The use of aqueous hydrochloric acid as the source of hydrogen chloride in the process of this invention is particularly advantageous as aqueous hydrochloric acid is commercially available and inexpensive, and is stable and may be stored for extended periods of time. Aqueous solutions may be used without the need for expensive specialised equipment such as that required to handle hydrogen chloride gas.
In the most general aspect of the invention, a solution of paroxetine base, or a salt of paroxetine with an organic acid, in an organic solvent is treated with aqueous hydrochloric acid. The solution is then distilled to reduce the amount of water present and is then treated with acetone to afford paroxetine hydrochloride acetone solvate as a crystalline solid.
A suitable organic acid is acetic acid
Suitable solvents for the paroxetine free base or salt are acetone miscible solvents in which paroxetine free base and paroxetine hydrochloride are soluble. Suitable solvents include: hydrocarbons for example toluene, xylene or heptane; esters for example ethylacetate or methylacetate; nitriles for example acetonitrile; ethers for example dioxane or tetrahydrofuran; halogenated hydrocarbons for example dichloromethane or chloroform and alcohols for example ethanol or propanol.
Preferred solvents are solvents which form an azeotrope with water and additionally do not form a solvate with paroxetine hydrochloride anhydrate Form A and hence do not compete with acetone as solvate molecules during the crystallization of paroxetme hydrochloride acetone solvate.
A particularly preferred solvent on a manufacturing scale is toluene, as a solution of paroxetine free base in toluene may be carried forward from a previous manufacturing step.
A particularly preferred source of source of hydrochloric acid on a manufacturing scale is concentrated hydrochloric acid as this minimises the amount of water to be removed by distillation. Addition of the aqueous hydrochloric acid may be carried out at ambient or elevated temperature.
In a preferred aspect of the invention the paroxetine free base solution is treated with aqueous hydrochloric acid, then partial distillation is carried out in order to remove the water present as an azeotrope and the remaining solution is diluted with acetone to afford paroxetine hydrochloride acetone solvate as a crystalline solid.
The distillation of the paroxetine hydrochloride solution may be carried out at atmospheric, elevated or reduced pressure.
Treatment with acetone may be carried out at ambient, elevated or reduced temperature.
Paroxetme free base and salts may be prepared as described US 4,007, 196 or EP- 0,223,403.
In a further aspect of the invention paroxetine hydrochloride anhydrate Form A is manufactured by desolvating the acetone solvate by procedures described in WO 96/24595.
The paroxetine hydrochloride anhydrate Form A obtainable by this mvention may be used in therapy in formulations described in EP-A-0223403 or WO 96/00477.
Therapeutic uses of the paroxetine hydrochloride anhydrate obtainable by this invention include treatment of inter alia : alcoholism, anxiety, depression, obsessive compulsive disorder (OCD), 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". Most suitably the anhydrate obtainable by the present invention is applied to the treatment of depression, OCD and panic.
The compositions prepared in accordance with this invention are usually adapted for oral administration, but formulations for dissolution for parental administration are also within the scope of this invention.
The composition is usually presented as a unit dose composition containing from 1 to 200mg of active ingredient calculated on a free base basis, more usually from 5 to 100 mg, for example 10 to 50 mg such as 10, 12.5, 15, 20, 25, 30 or 40 mg by a human patient. Most preferably unit doses contain 20 mg of active ingredient calculated on a free base basis. Such a composition is normally taken from 1 to 6 times daily, for example 2, 3 or 4 times daily so that the total amount of active agent administered is within the range 5 to 400 mg of active ingredient calculated on a free base basis. Most preferably the unit dose is taken once a day.
Preferred unit dosage forms include tablets or capsules, including formulations adapted for controlled or delayed release.
The compositions of this invention may be formulated by conventional methods of admixture such as blending, filling and compressing. Suitable carriers for use in this invention include a diluent, a binder, a disintegrant, a colouring agent, a flavouring agent and/or preservative. These agents may be utilized in conventional manner, for example in a manner similar to that already used for marketed anti-depressant agents.
Specific examples of pharmaceutical compositions include those described EP-B- 0223403, and US 4,007,196 in which the anhydrate product of the present invention may be used as the active ingredient.
Accordingly, the present invention also provides: a pharmaceutical composition for treatment or prophylaxis of the Disorders comprising paroxetine hydrochloride anhydrate Form A obtainable by this invention and a pharmaceutically acceptable carrier;
the use of paroxetine hydrochloride anhydrate Form A obtainable by 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 Form A obtainable by this invention to a person suffering from one or more of the Disorders.
The invention is illustrated by the following Examples
Example 1
Concentrated hydrochloric acid (2.5 ml) was added to a stirred solution of paroxetine free base (10.0 g) in toluene (100 ml) and the mixture heated to 90°C for five minutes. Half of the total volume of solvent was removed by distillation under reduced pressure and dry acetone (50 ml) was added to the stirred mixture under a nitrogen atmosphere. The thick white suspension was allowed to cool to ambient temperature with stirring and the product collected by filtration and washed with acetone (20 ml) to give paroxetine hydrochloride acetone solvate (9.5 g).
IR (nujol mull) bands at cm"1: 3633, 3401, 1715, 1631, 1604, 1563, 1547, 1512, 1492, 1467, 1287, 1249, 1221, 1193, 1162, 1132, 1091, 1068, 1035, 1004, 968, 924, 908, 886, 831, 806, 783, 762, 721, 666, 614, 593, 572, 538.
The product was dried under vacuum at 60°C for 20 hours to give a product with an acetone content of 1.3 % by wt, as determined by 1H-NMR.
Example 2 A stirred mixture of N-phenoxycarbonyl paroxetine (19.4 g), potassium hydroxide (17.5 g) and toluene (300 ml) is heated to reflux under a nitrogen atmosphere for 3 hours. The mixture is cooled to room temperature, washed with water (200 ml) and the organic layer separated, dried over magnesium sulphate and concentrated to a total volume of 150 ml. Concentrated hydrochloric acid (3.5 ml) is added to the solution and the mixture stirred and heated to 75°C. The total volume of the reaction mixture is reduced to half by distillation under reduced pressure and dry acetone (75 ml) is added to the stirred reaction mixture, under a nitrogen atmosphere. The mixture is cooled to ambient temperature, stirred for 30 minutes and the product collected by filtration, washed with acetone (30 ml) and dried under vacuum at 60°C for 20 hours.

Claims

1. A process for preparing paroxetine hydrochloride acetone solvate, in which a solution of paroxetine base, or a salt of paroxetine with an organic acid, in an organic solvent is treated with aqueous hydrochloric acid, the solution is distilled to reduce the amount of water present and is then treated with acetone to afford paroxetine hydrochloride acetone solvate as a crystalline solid.
2. A process according to claim 1 in which the solvent for the paroxetine free base or salt is selected from: hydrocarbons for example toluene, xylene or heptane; esters for example ethylacetate or methylacetate; nitriles for example acetonitrile; ethers for example dioxane or tetrahydrofuran; halogenated hydrocarbons for example dichloromethane or chloroform and alcohols for example ethanol or propanol.
3. A process according to claim 1 or 2 in which concentrated hydrochloric acid is used.
4. A process according to any one of claims 1 to 3 in which the paroxetine free base solution is treated with aqueous hydrochloric acid, then partial distillation is carried out in order to remove the water present as an azeotrope and the remaining solution is diluted with acetone to afford paroxetine hydrochloride acetone solvate as a crystalline solid.
5. A process according to any one of claims 1 to 4 in which the crystalline product is desolvated to obtain paroxetine hydrochloride anhydrate Form A.
6. A method of treating the Disorders which comprises administering an effective or prophylactic amount of paroxetine hydrochloride anhydrate Form A obtainable by this invention to a person suffering from one or more of the Disorders.
PCT/GB2000/003802 1999-10-04 2000-10-04 Process for the preparation of paroxetine hydrochloride acetone solvate WO2001025232A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU75428/00A AU7542800A (en) 1999-10-04 2000-10-04 Process for the preparation of paroxetine hydrochloride acetone solvate

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9923439.5 1999-10-04
GBGB9923439.5A GB9923439D0 (en) 1999-10-04 1999-10-04 Novel process

Publications (1)

Publication Number Publication Date
WO2001025232A1 true WO2001025232A1 (en) 2001-04-12

Family

ID=10862092

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2000/003802 WO2001025232A1 (en) 1999-10-04 2000-10-04 Process for the preparation of paroxetine hydrochloride acetone solvate

Country Status (3)

Country Link
AU (1) AU7542800A (en)
GB (1) GB9923439D0 (en)
WO (1) WO2001025232A1 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996024595A1 (en) * 1995-02-06 1996-08-15 Smithkline Beecham Plc New forms of paroxetin hydrochloride
WO1998031365A1 (en) * 1997-01-15 1998-07-23 Smithkline Beecham Plc Paroxetine compositions
WO1999032484A1 (en) * 1997-12-19 1999-07-01 Smithkline Beecham Plc Process for the preparation of paroxetine hydrochloride
WO2000032595A1 (en) * 1998-11-30 2000-06-08 Smithkline Beecham Plc Process for the production of paroxetine hydrochloride acetone solvate

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996024595A1 (en) * 1995-02-06 1996-08-15 Smithkline Beecham Plc New forms of paroxetin hydrochloride
WO1998031365A1 (en) * 1997-01-15 1998-07-23 Smithkline Beecham Plc Paroxetine compositions
WO1999032484A1 (en) * 1997-12-19 1999-07-01 Smithkline Beecham Plc Process for the preparation of paroxetine hydrochloride
WO2000032595A1 (en) * 1998-11-30 2000-06-08 Smithkline Beecham Plc Process for the production of paroxetine hydrochloride acetone solvate

Also Published As

Publication number Publication date
AU7542800A (en) 2001-05-10
GB9923439D0 (en) 1999-12-08

Similar Documents

Publication Publication Date Title
US5856493A (en) Process for making novel form of paroxeting hydrochloride anhydrate
EP1136490A1 (en) New forms of paroxetin hydrochloride
JP2002503248A (en) 4-phenylpiperidine compound
WO2003013529A1 (en) Paroxetine glycyrrhizinate
WO2000035873A1 (en) Process for preparation of paroxetine maleate
WO2000035910A1 (en) Derivative of paroxetine
WO2001025232A1 (en) Process for the preparation of paroxetine hydrochloride acetone solvate
WO2001025230A1 (en) Process for the preparation of paroxetine hydrochloride acetone solvate
EP1135383B1 (en) Mixed paroxetine propan-2-ol solvates
EP1089995A1 (en) Paroxetine ascorbate
WO2001017966A1 (en) Process for the preparation of 1-methyl-3-carbomethoxy-4-(4'-fluorophenyl)-piperidine
WO1999055699A1 (en) Paroxetine 10-camphorsulfonate for treatment of cns disorders
WO2000032595A1 (en) Process for the production of paroxetine hydrochloride acetone solvate
WO2001014369A2 (en) Process for the preparation of paroxetin.hcl
WO2001012623A1 (en) Process for the preparation of paroxetine hydrochloride
JP2002506865A (en) Crystal form of paroxetine
WO2001025231A1 (en) Process for the preparation of paroxetine hydrochloride acetone solvate
WO2001025201A1 (en) Process for the preparation of paroxetin intermediate
WO2000078752A1 (en) Process for the production of paroxetine hydrochloride
MXPA00010435A (en) Paroxetine 10-camphorsulfonate for treatment of cns disorders
WO2000032596A1 (en) Amine salts of paroxetine
EP1133492A1 (en) Process for the preparation of paroxetine hydrochloride

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 BY BZ CA CH CN CR CU CZ DE DK DM DZ EE 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 NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP