AU754765B2 - Paroxetine compositions - Google Patents
Paroxetine compositions Download PDFInfo
- Publication number
- AU754765B2 AU754765B2 AU30451/99A AU3045199A AU754765B2 AU 754765 B2 AU754765 B2 AU 754765B2 AU 30451/99 A AU30451/99 A AU 30451/99A AU 3045199 A AU3045199 A AU 3045199A AU 754765 B2 AU754765 B2 AU 754765B2
- Authority
- AU
- Australia
- Prior art keywords
- paroxetine
- pharmaceutically acceptable
- solid
- acceptable derivative
- adsorbed
- 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.)
- Withdrawn - After Issue
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Inorganic Chemistry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
PAROXETINE COMPOSITIONS The present invention relates to new formulations of a pharmaceutically active compound, and in particular to a novel formulation ofparoxetine.
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.
In the literature this compound is usually isolated as an acid salt, especially the hydrochloride. Paroxetine is approved for human use as the hydrochloride salt, and has been proposed for the treatment and prophylaxis of inter 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 W096/24595 of SmithKline Beecham).
Paroxetine free base has hitherto been disclosed in the literature as an oil, and so the free S. base has not itself been considered for therapeutic use, preference being given to S. crystalline forms which can be more easily purified and processes into dosage forms.
The present invention is based on the discovery that paroxetine, for example paroxetine 25 free base, is advantageously formulated into pharmaceutical compositions when adsorbed on or absorbed by a solid carrier.
The present invention provides a composition comprising paroxetine or a pharmaceutically acceptable derivative thereof adsorbed on or absorbed by a pharmaceutically acceptable solid non-polymeric carrier, and the use of the composition as a therapeutic agent or for the manufacture of a medicament.
WO 99/48499 PCT/GB99/00922 By this invention paroxetine may be obtained as a free-flowing powder that can be used directly (for example by direct compression into tablet form) or with further compounding ingredients in therapy.
The paroxetine used in carrying out this invention is preferably paroxetine free base, but may alternatively be a pharmaceutically acceptable derivative such as a salt, more especially the hydrochloride.
The composition of this invention is simply obtained by combining a solution of paroxetine with a suitable adsorbent or absorbent material and evaporating the solvent, for example by spray drying. The solvent is suitably toluene, ethanol, acetone, propan-2-ol, or ethyl acetate, or any other suitable solvent or mixture of solvents, in a paroxetine concentration of between 1 and 20%, more preferably between 1 and 4%.
Alternatively an oil obtained by removal of solvent from a solution may be blended with a solid adsorbent or absorbent material.
Typically the material selected as carrier for the paroxetine is an excipient suitable for tablet formation or as a fill material for gelatine capsules, such as cyclodextrin (beta and /or gamma), porous silicates, starch, lactose or calcium phosphate, silica, sorbitol, maltodextrin, microcrystalline or powdered cellulose, sodium or calcium carboxymethylcellulose, calcium carbonate, kaolin, magnesium aluminium silicate.
Additionally, soluble excipients such as magnesium stearate may form part of the solution phase.
Advantageously the carrier is one that also has a taste-masking effect, for example ionexchange resins.
A solution of paroxetine free base may be prepared by addition of a base such as triethylamine to a solution of a crystalline paroxetine salt especially the hydrochloride or acetate. Alternatively the solution may be prepared by basifying a solution of an WO 99/48499 PCT/GB99/00922 amorphous paroxetine hydrochloride or a crystalline anhydrate or hydrated form of paroxetine hydrochloride.
The preparation of the free base and the maleic acid salt are 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.
Additionally the paroxetine free base may be prepared as a solution or oil by adding a base such as potassium hydroxide to a solution of a N-protected paroxetine compound such as N-phenoxycarbonyl paroxetine.
The composition of this invention comprising paroxetine adsorbed on or absorbed by a solid carrier may be formulated with or without conventional excipients for tablet formation or used 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. Preferably the unit dose contains from to 100 mg paroxetine (as measured in terms of the free base). More preferable the amount of paroxetine in a unit dose is 10mg, 20mg, 30mg, 40mg or 50mg. The most preferred amount of paroxetine in a unit dose is 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, pre-menstrual 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 or a pharmaceutically acceptable derivative thereof adsorbed on or absorbed by a solid carrier and, optionally, at least one further pharmaceutically acceptable excipient; WO 99/48499 PCT/GB99/00922 the use of paroxetine or a pharmaceutically acceptable derivative thereof adsorbed on or absorbed by a solid carrier 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 or a pharmaceutically acceptable derivative thereof adsorbed on or absorbed by a solid carrier to a person suffering from one or more of the disorders.
The invention is illustrated by the following Examples: Example 1. Preparation of tablet pre-mix containing paroxetine free base.
A mixture of dibasic calcium phosphate dihydrate (408 hydroxypropylmethyl cellulose (25 g) and sodium starch glycollate (25 g) was blended in a key granulator for 3 minutes at a stir rate of 240 r.p.m. and an impeller rate of 3000 r.p.m. Purified water (57 ml) was added at a rate of approximately 4 ml/minute for 13.5 minutes while the key granulator was set at a stir rate of 240 r.p.m. and the impeller rate was set at 1500 r.p.m.
The mixture was stirred for a further 1 minute, and the resulting granules dried in an air oven at 50°C for 3 hours.
A portion of the granules prepared above (50 g) was added to a solution of paroxetine free base (2.0 g) in propan-2-ol (50 ml) and the resulting slurry dried under vacuum with agitation at 50 0
C.
This product is suitable for direct compression into tablets containing 10, 20, or 30 mg paroxetine.
Example 2. Preparation of a solid supported form of paroxetine free base.
A stirred mixture of N-phenoxycarbonyl paroxetine 50.0g potassium hydroxide (45.0g) and toluene 750ml) was heated to reflux under a nitrogen atmosphere for 3 hours. After allowing the mixture to cool to room temperature, distilled water (500ml) was added and the mixture stirred for 30 minutes. The organic layer was separated, dried over magnesium sulfate and concentrated to a total volume of Toluene (100ml) was added to an aliquot of the solution of paroxetine free amine in toluene 0.43g/ml) (2.4 ml) and to this solution was added Celite 25.0g and WO 99/48499 PCT/GB99/00922 the mixture stirred for 5 minutes. Solvent was removed under reduced pressure (water bath 55 0 C) to afford the Celite supported paroxetine free amine as a free moving powdery solid (26.0g).
This product may be mixed with additional excipients and compressed into tablets or added directly to capsule shells to make a product containing a therapeutic dose of paroxetine.
Example 3 Spray drying of paroxetine hydrochloride solution onto a suspended carrier material.
Anhydrous paroxetine hydrochloride (60 g) was dissolved in anhydrous ethanol (725 ml) and the clear solution slurried with maltodextrin DE4-6 (506 The uniform suspension was spray-dried in a Niro Mobile Minor (TM) closed cycle spray dryer using nitrogen as the process gas, a rotary atomiser wheel spinning at 27,000 r.p.m. (alternatively a cocurrent or fountain two-fluid nozzle could be used), an inlet temperature of 96-104 C and outlet temperature of 44-50 C at a feed rate of 4.1 kg per hour. A white free-flowing product was recovered (490 g) which was found to have a mean particle size of 84 microns.
Example 4 Preparation of tablet pre-mix containing paroxetine hydrochloride.
A mixture of dibasic calcium phosphate dihydrate (408 hydroxypropylmethyl cellulose (25 g) and sodium starch glycollate (25 g) was blended in a key granulator for 3 minutes at a stir rate of 240 r.p.m. and an impeller rate of 3000 r.p.m. Purified water (57 ml) was added at a rate of approximately 4ml/minute for 13.5 minutes while the key granulator was set at a stir rate of 240 r.p.m. and the impeller rate was set at 1500 r.p.m.
The mixture was stirred for a further 1 minute, and the resulting granules dried in an air oven at 50°C for 3 hours.
A solution of paroxetine hydrochloride hemihydrate (2.0 g) in ethanol (100 ml) was added to the granules prepared above (50 g) and the slurry dried under vacuum at 50 0
C.
Example Preparation of tablet pre-mix containing paroxetine hydrochloride.
WO 99/48499 PCT/GB99/00922 A solution of paroxetine hydrochloride hemihydrate (2.0 g) in ethanol (150 ml) was added to celite (50 the mixture stirred and the slurry dried under vacuum at 50 0 C to afford a free moving powdery solid, suitable for use as a component of a tablet or capsule formulation.
Example 6 Preparation of tablet pre-mix containing paroxetine hydrochloride.
A stirred mixture ofN-phenoxycarbonyl paroxetine 50.0 potassium hydroxide (45.0 g) and toluene 750 ml) was heated to reflux under a nitrogen atmosphere for 3 hours. After allowing the mixture to cool to room temperature, distilled water (500 ml) was added and the mixture stirred for 30 minutes. The organic layer was separated, dried over magnesium sulphate and filtered.
An aliquot of this solution of paroxetine free amine in toluene 0.048 g/ml] 21.0 ml) was diluted with a further 30 ml of toluene and heated to 600C. Concentrated hydrochloric acid (0.34 ml) was added and the mixture stirred for 10 minutes.
Tablet granules 25.0g prepared as in Example 4, were added and the mixture stirred at 60 0 C for 5 minutes. Solvent was removed under reduced pressure at 0 C to afford a mobile powdery solid (26.0g).
Example 7 Preparation of tablet pre-mix containing paroxetine hydrochloride.
Concentrated hydrochloric acid (0.34ml) was added to a stirred solution of paroxetine acetate (1.18g) in toluene (50ml) at 60 0 C and the mixture stirred for 10 minutes. Tablet granules 25.0g prepared as in Example 4, were added and the mixture stirred at 60 0
C
for 5 minutes. Solvent was removed under reduced pressure at 70 0 C to afford a free flowing powdery solid (26.0g).
Claims (11)
1. Paroxetine or a pharmaceutically acceptable derivative thereof adsorbed on or absorbed by a solid, non-polymeric carrier.
2. A pharmaceutical composition comprising paroxetine or a pharmaceutically acceptable derivative thereof adsorbed on or absorbed by a solid, non-polymeric carrier.
3. Use of a paroxetine or a pharmaceutically acceptable derivative thereof adsorbed on or absorbed by a solid, non-polymeric carrier to manufacture a medicament for the treatment of depression.
4. A method of treating depression which comprises administering an effective .*amount of paroxetine or a pharmaceutically acceptable derivative thereof adsorbed on or 15 absorbed by a solid, non-polymeric carrier to a person suffering from depression.
A composition of matter, use or method according to any one of the claims 1 to 4 S. wherein the paroxetine is in the form of its free base. 20
6. A process for the preparation of a composition of matter according to any one of claims 1, 2 or 5, which process comprises combining a solution of paroxetine or a i. pharmaceutically acceptable derivative thereof with the adsorbent or absorbent solid carrier material and evaporating solvent.
7. A process according to claim 6, wherein the carrier material is suspended in the solvent prior to evaporation of the solvent.
8. A process according to claim 6, wherein the carrier material is dissolved in the solvent prior to evaporation of the solvent.
9. A process according to any one of claims 6 or 8, wherein the evaporation of the S7solvent is carried out by spray drying.
P:\OPER\MaIl2002\30451-99 262.doc.239/19)2 Paroxetine or a pharmaceutically acceptable derivative thereof according to claim 1, wherein the solid non-polymeric carrier is calcium phosphate.
11. A paroxetine or a pharmaceutically acceptable derivative thereof which has been adsorbed on or absorbed by a solid, non-polymeric carrier, substantially as hereinbefore described with reference to the examples. DATED this 19 day of September, 2002 SmithKline Beecham p.l.c. By DAVIES COLLISON CAVE 15 Patent Attorneys for the Applicants *o
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2003200534A AU2003200534B2 (en) | 1998-03-24 | 2003-02-17 | Paroxetine compositions |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9806312.6A GB9806312D0 (en) | 1998-03-24 | 1998-03-24 | Novel formulations |
| GB9806312 | 1998-03-24 | ||
| PCT/GB1999/000922 WO1999048499A1 (en) | 1998-03-24 | 1999-03-24 | Paroxetine compositions |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2003200534A Division AU2003200534B2 (en) | 1998-03-24 | 2003-02-17 | Paroxetine compositions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU3045199A AU3045199A (en) | 1999-10-18 |
| AU754765B2 true AU754765B2 (en) | 2002-11-21 |
Family
ID=10829181
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU30451/99A Withdrawn - After Issue AU754765B2 (en) | 1998-03-24 | 1999-03-24 | Paroxetine compositions |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP1063993A1 (en) |
| JP (1) | JP2002507569A (en) |
| CN (1) | CN1125639C (en) |
| AP (1) | AP2000001914A0 (en) |
| AU (1) | AU754765B2 (en) |
| BG (1) | BG104865A (en) |
| BR (1) | BR9908991A (en) |
| CA (1) | CA2324612A1 (en) |
| EA (1) | EA003393B1 (en) |
| GB (1) | GB9806312D0 (en) |
| HU (1) | HUP0101326A3 (en) |
| ID (1) | ID26485A (en) |
| IL (1) | IL138478A0 (en) |
| NO (1) | NO313404B1 (en) |
| NZ (1) | NZ506893A (en) |
| PL (1) | PL343095A1 (en) |
| SK (1) | SK14102000A3 (en) |
| TR (1) | TR200002750T2 (en) |
| WO (1) | WO1999048499A1 (en) |
| ZA (1) | ZA200005697B (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9914600D0 (en) * | 1999-06-22 | 1999-08-25 | Smithkline Beecham Plc | Novel,process |
| DK200100341A (en) * | 2001-03-02 | 2002-09-03 | Gea Farmaceutisk Fabrik As | Process for the preparation of pharmaceutical tablets containing paroxetine hydrochloride anhydrate |
| EP1643975A2 (en) * | 2003-07-02 | 2006-04-12 | Abbott Laboratories | Process for preparing formulations of lipid-regulating drugs |
| US8062664B2 (en) | 2003-11-12 | 2011-11-22 | Abbott Laboratories | Process for preparing formulations of lipid-regulating drugs |
| HU1000278D0 (en) * | 2010-05-28 | 2010-07-28 | Egis Gyogyszergyar Nyilvanosan | Novel pharmaceutical use uf silicic acid |
| CN103961333B (en) * | 2014-05-07 | 2020-02-21 | 浙江华海药业股份有限公司 | Paroxetine mesylate capsule and preparation method thereof |
| CN104027306A (en) * | 2014-06-25 | 2014-09-10 | 万特制药(海南)有限公司 | Paroxetine oral suspension and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4007196A (en) * | 1973-01-30 | 1977-02-08 | A/S Ferrosan | 4-Phenylpiperidine compounds |
| EP0223403B1 (en) * | 1985-10-25 | 1993-08-04 | Beecham Group Plc | Piperidine derivative, its preparation, and its use as medicament |
| EP0810224A1 (en) * | 1996-05-30 | 1997-12-03 | Asahi Glass Company Ltd. | Method of producing amorphous paroxetine hydrochloride |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR001982A1 (en) * | 1995-02-06 | 1998-01-07 | Smithkline Beecham Plc | PAROXETINE CHLORHYDRATE ANHYDRATED, AND PROCEDURE FOR ITS PREPARATION |
-
1998
- 1998-03-24 GB GBGB9806312.6A patent/GB9806312D0/en not_active Ceased
-
1999
- 1999-03-24 EP EP99911940A patent/EP1063993A1/en not_active Withdrawn
- 1999-03-24 TR TR2000/02750T patent/TR200002750T2/en unknown
- 1999-03-24 EA EA200000977A patent/EA003393B1/en not_active IP Right Cessation
- 1999-03-24 NZ NZ506893A patent/NZ506893A/en unknown
- 1999-03-24 AU AU30451/99A patent/AU754765B2/en not_active Withdrawn - After Issue
- 1999-03-24 WO PCT/GB1999/000922 patent/WO1999048499A1/en not_active Application Discontinuation
- 1999-03-24 IL IL13847899A patent/IL138478A0/en unknown
- 1999-03-24 JP JP2000537547A patent/JP2002507569A/en active Pending
- 1999-03-24 PL PL99343095A patent/PL343095A1/en unknown
- 1999-03-24 SK SK1410-2000A patent/SK14102000A3/en unknown
- 1999-03-24 CA CA002324612A patent/CA2324612A1/en not_active Abandoned
- 1999-03-24 HU HU0101326A patent/HUP0101326A3/en unknown
- 1999-03-24 CN CN99804347A patent/CN1125639C/en not_active Expired - Fee Related
- 1999-03-24 AP APAP/P/2000/001914A patent/AP2000001914A0/en unknown
- 1999-03-24 ID IDW20001883A patent/ID26485A/en unknown
- 1999-03-24 BR BR9908991-2A patent/BR9908991A/en not_active IP Right Cessation
-
2000
- 2000-09-22 NO NO20004740A patent/NO313404B1/en unknown
- 2000-10-16 ZA ZA200005697A patent/ZA200005697B/en unknown
- 2000-10-16 BG BG104865A patent/BG104865A/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4007196A (en) * | 1973-01-30 | 1977-02-08 | A/S Ferrosan | 4-Phenylpiperidine compounds |
| EP0223403B1 (en) * | 1985-10-25 | 1993-08-04 | Beecham Group Plc | Piperidine derivative, its preparation, and its use as medicament |
| EP0810224A1 (en) * | 1996-05-30 | 1997-12-03 | Asahi Glass Company Ltd. | Method of producing amorphous paroxetine hydrochloride |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1063993A1 (en) | 2001-01-03 |
| NO313404B1 (en) | 2002-09-30 |
| IL138478A0 (en) | 2001-10-31 |
| CA2324612A1 (en) | 1999-09-30 |
| AU3045199A (en) | 1999-10-18 |
| BG104865A (en) | 2001-05-31 |
| TR200002750T2 (en) | 2000-12-21 |
| ID26485A (en) | 2001-01-11 |
| CN1125639C (en) | 2003-10-29 |
| WO1999048499A1 (en) | 1999-09-30 |
| NO20004740L (en) | 2000-10-03 |
| HUP0101326A2 (en) | 2002-05-29 |
| JP2002507569A (en) | 2002-03-12 |
| SK14102000A3 (en) | 2001-03-12 |
| PL343095A1 (en) | 2001-07-30 |
| BR9908991A (en) | 2000-12-12 |
| EA200000977A1 (en) | 2001-02-26 |
| NZ506893A (en) | 2003-06-30 |
| AP2000001914A0 (en) | 2000-09-30 |
| CN1294512A (en) | 2001-05-09 |
| HUP0101326A3 (en) | 2002-06-28 |
| EA003393B1 (en) | 2003-04-24 |
| ZA200005697B (en) | 2001-10-02 |
| GB9806312D0 (en) | 1998-05-20 |
| NO20004740D0 (en) | 2000-09-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| CB | Opposition filed |
Opponent name: MARK JAGGERS |
|
| CFC | Opposition proceedings - application withdrawn |
Opponent name: MARK J JAGGERS |
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| MK12 | Application lapsed section 141(1)/reg 8.3(2) - applicant filed a written notice of withdrawal |