GB2491023A - The preparation of paroxetine hydrochloride hemihydrate that is free from discolouration - Google Patents
The preparation of paroxetine hydrochloride hemihydrate that is free from discolouration Download PDFInfo
- Publication number
- GB2491023A GB2491023A GB1208567.6A GB201208567A GB2491023A GB 2491023 A GB2491023 A GB 2491023A GB 201208567 A GB201208567 A GB 201208567A GB 2491023 A GB2491023 A GB 2491023A
- Authority
- GB
- United Kingdom
- Prior art keywords
- paroxetine hydrochloride
- hydrochloride hemihydrate
- zetacarbon
- paroxetine
- process according
- 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.)
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- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 title claims abstract 21
- 229960002296 paroxetine Drugs 0.000 title claims abstract 21
- 238000002360 preparation method Methods 0.000 title claims abstract 7
- 238000000034 method Methods 0.000 claims abstract 19
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims abstract 7
- 230000002378 acidificating effect Effects 0.000 claims abstract 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract 3
- AHOUBRCZNHFOSL-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidine Chemical compound C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 claims 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims 2
- 229960005183 paroxetine hydrochloride Drugs 0.000 claims 1
- 239000002245 particle Substances 0.000 claims 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 abstract 9
- 238000001914 filtration Methods 0.000 abstract 2
- 239000007787 solid Substances 0.000 abstract 2
- 238000001816 cooling Methods 0.000 abstract 1
- 239000000706 filtrate Substances 0.000 abstract 1
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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A process for the preparation of paroxetine hydrochloride hemihydrate that is substantially free from discolouration comprises treating discoloured paroxetine hydrochloride hemihydrate with one or more of an acidic alumina or a 3M Zetacarbon. The treatment may occur in solution (e.g. alcohol, IPA, IMS). Pink coloured paroxetine hydrochloride hemihydrate was slurred in 5% aqueous IPA (isopropyl alcohol) and heated to 70°C-75°C. Alumina was added. Subsequent filtration gave a clear, colourless filtrate. Upon cooling and filtration, a white to off-white crystalline solid (paroxetine hydrochloride hemihydrate) was obtained. The use of Zetacarbon type R55SP resulted in paroxetine hydrochloride hemihydrate as a white crystalline solid.
Description
PROCESS
Field of the Invention
The present invention relates to a process for the preparation of paroxetine, and salts and solvates thereof.
More particularly, the invention relates to a process for the preparation of paroxetine, and salts and solvates thereof, that prevents or removes any undesirable pink colouration. The invention especially relates to a process for the preparation of paroxetine hydrochloride hemihydrate.
Background to the Invention
Paroxetine is chemically known as (-)-trans-4R-(4t-fluorophenyl)-3S-[(3t,4'-methylenedioxyphenoxy) methyl] piperidine. The structural formula of paroxetine freebaseis: It is an orally administered psychotropic drug which is an SSRI (Selective Serotonin Reuptake Inhibitor) marketed as Paxil® and Seroxat® for the treatment of, inter alia, depression, obsessive compulsive disorder (OCD), panic disorder, anxiety and post-traumatic stress disorder. Paroxetine is an off-white powder and is generally sold and administered as the hydrochloride salt of the hemihydrate in a solid dosage form as a film-coated tablet. Tablets containing 10mg of paroxetine hydrochloride hemihydrate, equivalent to paroxetine, are yellow film coated tablets; 20 mg are pink; mg are blue and 40 mg are green.
In 2007, paroxetine has sales in excess of US $1 billion, and in 2006, paroxetine was the fifth-most prescribed antidepressant in the USA with more than 19.7 million prescriptions.
It is well known in the art that a major problem in the manufacture of paroxetine hydrochloride hemihydrate is that the material can be contaminated with a pink colouration which renders it unsuitable for use as a pharmaceutically active ingredient.
US Patent No. 6,645,523 (Synthon) published on 30 May 2002 discloses that the colouration problem, i.e. the contamination with a pink hue, in tablets of paroxetine hydrochloride hemihydrate, involves the formation of a colouring impurity identified as compound A which is a dimer or paroxetine quinone adduct formed from paroxetine free base in an aqueous alkaline environment. F 0 cx'
Compound A, Paroxetine quinone adduct
I
US 523 discloses a solid paroxetine composition that resists the formation of a pink colouration by making the paroxetine in an aqueous environment and controlling the pH of the composition to 6.5 or less by the use of an acidic calcium phosphate.
US Patent Application No. 2006/216345 (Sun Pharmaceuticals Limited) published on 28 September 2006, describes a stable oral pharmaceutical composition of paroxetine hydrochloride hemihydrate formed by a conventional aqueous granulation process which prevents the formation of a pink colouration upon storage of the composition.
US Patent No. 6,113,944 (SmithKline Beecham) published on 5 September 2000, discloses that paroxetine formulated into a tablet using a process in which water is absent, is much less likely to develop a pink colouration upon storage.
International Patent Application No. WO 2005/034954 (Ranbaxy), published on 21 April 2005, discloses a paroxetine pharmaceutical composition prepared by a wet granulation technique which avoids the pink discolouration.
International Patent Application No. WO 2004/09 1582 (IPCA), published on 28 October 2004, describes a paroxetine composition wherein individual granules of paroxetine are coated with a moisture barrier which substantially eliminates the possibility of degradation or discolouration.
International Patent Application No. WO 02/102382 (Teva), published on 27 December 2002, describes a process for preparing paroxetine hydrochloride which comprises reacting paroxetine base with less than one molar base equivalent of hydrochloric acid and separating the paroxetine hydrochloride, thereby providing a paroxetine hydrochloride substantially free of pink coloured compounds.
International Patent Application No. WO 2004/026860 (Sumitomo), published on 1 April 2004, describes a method of precipitating crystals of paroxetine hydrochloride hemihydrate in a water-containing polar organic solvent, thereby precipitating crystals of paroxetine hydrochloride hemihydrate which are not coloured pink.
It is clear from the aforementioned prior art disclosures that the discolouration of paroxetine hydrochloride hemihydrate is not well understood.
Furthermore, each of the aforementioned prior art disclosures attempt to prevent the discolouration of paroxetine hydrochloride hemihydrate. However, none of the prior art disclosures disclose or teach the skilled person how to address the problem of discolouration once it has already occurred.
To the extent that the discolouration of paroxetine hydrochloride hemihydrates is understood, it is desirable to avoid the use of an acid environment, for example, it would be desirable to avoid the use of hydrochloric acid and /or chloride ions due to the corrosive nature of such materials. For any process that is developed to be used on a large scale, e.g. plant scale, it is desirable to eliminate conosion and to minimise waste streams.
Therefore there is a need for an improved method of preparing paroxetine hydrochloride hernihydrate and a need to be able to remove any pink discolouration if it is observed.
Summary of the Invention
It has been observed that paroxetine hydrochloride hemihydrate can fail on colour specification, i.e. it has a pink hue or discolouration when crystallisation occurs in the absence of hydrochloric acid. Investigations into the identity of the material causing the pink hue indicate that the colouration could be due to a quinone adduct being formed between a catechol impurity of paroxetine and paroxetine freebase (see scheme 1).
F OH
N
H
Paroxetine Catechol Impurity ?+ 0bTh_ 4o " H Paroxetine Freebase Paroxetine Quinone Adduct Scheme 1: Proposed formation of the paroxetine quinone adduct Thus, the addition of hydrochloric acid during the crystallisation step converts any freebase present in solution to the hydrochloride which prevents the formation of the quinone adduct.
We have found that treating discoloured paroxetine hydrochloride hemihydrate with conventionally known decolouring agents, such as conventional activated carbons, does not provide satisfactory results. However, we have surprisingly found that certain very specific decolouring agents are unexpectedly capable of removing the discolouration from paroxetine hydrochloride hemihydrate.
Therefore, according to a first aspect of the present invention there is provided a process for the preparation of paroxetine hydrochloride hemihydrate that is substantially free from discolouration, which comprises treating discoloured paroxetine hydrochloride hemihydrate with one or more of an acidic alumina or a 3M Zetacarbon®.
According to one aspect of the invention there is provided a process comprising the preparation of paroxetine hydrochloride hemihydrate that is substantially free from discolouration, by treating the discoloured paroxetine hydrochloride hemihydrate with a 3M Zetacarbon®.
According to a further aspect of the invention there is provided a process comprising the preparation of paroxetine hydrochloride hemihydrate that is substantially free from discolouration, by treating the discoloured paroxetine hydrochloride hemihydrate with an acidic alumina.
The acidic alumina (aluminium oxide Al203) will generally have a pH of 4.5±0.5.
The particle size may vary, but will generally comprise particles of from about 0.05 to about 0.15mm diameter particles.
Investigations into the water content of paroxetine hydrochloride hemihydrate have shown that minor variation in the water charge and the use of a 3M Zetacarbon® cartridges has no impact.
3M Zetacarbon® is an activated carbon available in the UK from Cuno Limited.
Zetacarbon® filters are available in five standard carbon grades, each with three different filtration settings. Therefore, the person skilled in the art can select from one or more of 15 different Zetacarbon® filters, e.g. R11SP, R12SP, R13SP, R14SP, R1SSP, R31SP, R32SP, R33SP, R34SP, R3SSP, RS1SP, R52SP, RS3SP, R54SP and R55SP. Thus, for example, Zetacarbon® discs are available with a "5" filtration rating with different carbon grades, as grade R51SP, RS2SP, R53SP, R54SP and R5SSP.
In an especially preferred aspect of the present invention the Zetacarbon® comprises a carbon grade of R55SP.
Although Zetacarbon® and/or acidic alumina as hereinbefore described may be available in a variety of forms, Zetacarbon® is available as, inter alia, filter elements.
We have found that when using Zetacarbon®, the number of filter elements in the process of the present invention may be varied, i.e. may be one or more. Preferably more than one ifiter element is used. For example from 1 to 10 ifiter elements may be used, preferably from 2 to 8, preferably from 3 to 6, more preferably from 3 to 5 filter elements may be used. We have especially found that 4 elements may provide the optimum decolouration whilst providing a financially viable process. When more than one Zetacarbon® ifiter element is used, the filter elements may be the same or different. Preferably, the ifiter elements are the same, i.e. preferably Zetacarbon® R55SP filter elements.
For treatment with Zetaca±bon® and/or acidic alumina the paroxetine hydrochloride hemihydrate is in solution. Generally, the paroxetine hydrochloride hemihydrate solution may utilise a variety of solvents. However, a preferred solvent is an alcohol, e.g. an alkyl Cl to 10 alcohol, preferably an aqueous alcohol. Especially preferred solvents include IMS (industrial methylated spirits)! water or WA (isopropyl alcohol)! water. Preferably, the IMS/ water or WA! water is present in a ratio of (95:5 v/v).
For use on a plant scale a continuous or semi-continuous flow of a solution of paroxetine hydrochloride hemihydrate through one or more Zetacarbon® or alumina filter elements. In such a process the flow rate may be from about 1 to about 50 Llmin, preferably from about 5 to about 45 IJmin, preferably from about 10 to about 40 Iimin, preferably from about 15 to about 35 IJmin, preferably from about 20 to about 30 IJmin, e.g. about 25 Jimin.
The process of the present invention is advantageous in that, inter alia, any of the prior art methods for the preparation of paroxetine hydrochloride hemihydrate may be used and may be modified according to the teachings of the present invention to remove any discolouration.
According to a further aspect of the invention there is provided paroxetine hydrochloride hemihydrate wherein any discolouring agents have been substantially removed, i.e. the level of discolouring agents is about zero or is undetectable.
Such discolouring agents include, but shall not be limited to, paroxetine quinone adduct as hereinbefore described and refened to as compound of formula A in US Patent No. 6,645,523. Thus, this aspect of the invention especially provides paroxetine hydrochloride hemihydrate wherein any paroxetine quinone adduct has been substantially removed, i.e. the level of paroxetine quinone adduct is about zero
or is undetectable.
The colouration or the disappearance of the colouration (the decolouration) of paroxetine hydrochloride hemihydrate may be determined by a variety of methods known to the person skilled in the art. Thus, for example, decolouration may be determined by one or more of visual inspection, UV/vis spectrophotometry, etc. Alternatively, the purity of the paroxetine hydrochloride hemihydrate may be determined by measuring the levels of discolouring impurities hereinbefore defined, especially paroxetine quinone adduct using conventionally known techniques known in the art, such as, for example, HPLC etc. As used herein, the term "pink't has its ordinary meaning and refers to any of a group of colours reddish in hue, of medium to high lightness, and of low to moderate saturation. Thus, reference to, for example, discolouring agents being undetectable shall be understood to mean not detectable by one or more of the aforementioned analytical methods.
According to the present invention, the paroxetine hydrochloride hemihydrate in which any discolouring agents have been substantially removed, prepared by the methods disclosed herein can be prepared as pharmaceutical compositions that are particularly useful for inhibiting the re-uptake of serotonin. Such compositions can include paroxetine hydrochloride hemihydrate in combination with pharmaceutically acceptable carriers and/or excipients known to the person skilled in the art.
For example, these compositions may be prepared as medicaments to be administered orally, parenterally, rectally, transdermally, bucally, or nasally. Suitable forms for oral administration include tablets, compressed or coated pills, dragees, sachets, hard or gelatin capsules, sub-lingual tablets, syrups and suspensions. Suitable forms of parenteral administration include an aqueous or non-aqueous solution or emulsion, while for rectal administration suitable forms for administration include suppositories with a hydrophilic or a hydrophobic vehicle. For topical administration, suitable transdermal delivery systems known in the art, and for nasal delivery, suitable aerosol delivery systems known in the art, may be employed.
A particularly preferred dosage form is a coated tablet. Such tablet contains a pharmaceutically effective amount of the paroxetine hydrochloride hemihydrate of the present invention in conjunction with one or more excipients, such as a binder, filler, stabilizer, disintegrant, glidant, flavouring and colouring agents. An effective amount of paroxetine hydrochloride hemihydrate is approximately from about 10 mg to about mg of the base equivalent of paroxetine, for example, as disclosed in US Patent No. 6,080,759, preferably from about 10mg to about 40mg.
Suspensions, containing a dosage of about 10 mg of the base equivalent of paroxetine per Sml of liquid are also included within the scope of the pharmaceutical compositions of the present invention. The effective dose for the suspension is about the same as that for the tablet.
The prescribing information for Paxil® and Seroxat® can be used as guidance for both dosage and formulation of the paroxetine hydrochloride hemihydrate of the present invention.
The invention will now be illustrated by way of example only.
EXAMPLES
EXAMPLE 1
Pure paroxetine hydrochloride hemihydrate (pink coloured, 50,g) was slurried in 5% aqueous IPA (isopropyl alcohol) (250g) and heated to between 70°C and 75°C for 1 hour to ensure full dissolution. Brockmann alumina (4.2g) was added to the clear pink solution and the resulting slurry stirred for 2 hours. The alumina was removed by filtration to give clear, colourless filtrates. The filtrates were cooled to 3°C and stirred for 1 hour. The resulting precipitate was isolated by filtration and dried in a vacuum oven at 30°C for 18 hours to yield paroxetine hydrochloride hemihydrate as a white to off-white crystalline solid. It was noted that the alumina had taken on the pink colouration, suggesting that the removal of the colour from the paroxetine hydrochloride hemihydrate was by a process of absorption/adsorption rather than an acidic effect.
EXAMPLE 2
Crude paroxetine hydrochloride (SOg) was slurried in 5% aqueous IPA (250g) and heated to between 70°C and 75°C for 1 hour to ensure full dissolution. Brockmann alumina (4.2g) was added to the clear solution and the resulting slurry stirred for 2 hours. The alumina was removed by filtration to give clear, colourless filtrates. The filtrates were cooled to 60°C and stirred for 1 hour. A seed of pure paroxetine hydrochloride hemihydrate was added and the mixture stirred for 30 minutes. The resulting slurry was cooled to 45°C over 2 hours and cooled further to -5°C over 2 hours. The mixture was stirred at this temperature for 18 hours and the resulting precipitate isolated by filtration and dried in a vacuum oven at 30°C for 18 hours to yield paroxetine hydrochloride hemihydrate as a white crystalline solid. It was noted that the alumina had taken on the pink colouration.
EXAMPLE 3
Crude paroxetine hydrochloride (40g) was slurried in 5% aqueous IPA (200g) and heated to between 70°C and 75°C for 2 hours. Zetacarbon® Type RSSSP (2.7g) was added to the clear solution and the resulting slurry stirred for 2 hours. The carbon was removed by filtration and the filter cake washed with IPA (12g). The filtrates were heated to 75°C to ensure full dissolution, then cooled to 60°C. A seed of pure paroxetine hydrochloride hemihydrate was added and the mixture stirred for 30 minutes. The resulting slurry was cooled to 45°C over 2 hours and cooled further to -5°C over 2 hours. The mixture was stirred at this temperature for 60 minutes and the resulting precipitate isolated by filtration, washed twice with 5% aqueous IPA (11.2g) and dried in a vacuum oven at 50°C for 6 hours to yield paroxetine hydrochloride hemihydrate as a white crystalline solid.
EXAMPLE 4
Crude paroxetine hydrochloride (120g) was slurried in 5% aqueous IPA (642.4g) and heated to between 70°C and 75°C for 2 hours. The resulting solution was passed through a Zetacarbon® cartridge housed in a Cuno' at a flow rate of 25mL/min.
The cartridge was washed with WA (l2g). The filtrates were heated to 75°C to ensure full dissolution, then cooled to 60°C. A seed of pure paroxetine hydrochloride hemihydrate was added and the mixture stirred for 30 minutes. The resulting slurry was cooled to 45°C over 2 hours and cooled further to -5°C over 2 hours. The mixture was stirred at this temperature for 60 minutes and the resulting precipitate isolated by filtration, washed twice with 5% aqueous IPA (1 l.2g) and dried in a vacuum oven at 30°C for 18 hours to yield paroxetine hydrochloride hemihydrate as a white crystalline solid.
EXAMPLE 5
Deionised Water (70kg), IPA (1492.5kg) and crude paroxetine hydrochloride (249kg), were charged to a reactor vessel and the mixture heated to 75.5°C for 30 minutes.
The resulting clear solution was transferred to a second vessel via a Cuno filter containing four RSSSP filter cartridges over 94 minutes (about 23L/min) followed by an WA wash (50kg). The solution was reheated to 72.5°C to ensure that all material remained in solution. The solution was cooled to 61.5°C and a seed of pure paroxetine hydrochloride hernihydrate (0.15kg) was added and the mixture stirred for 240 minutes, maintaining the temperature between 59.5°C and 61.5°C. The resulting slurry was cooled to 1.4°C over 160 minutes and stirred at this temperature for a further 120 minutes. The slurry was transferred to a filter dryer followed by an IPA S wash (123.8kg) The precipitate was isolated by filtration and the filter cake washed twice with 5% aqueous ifiA (103kg). The product was dried under intermittent stirring at 35.5°C for 6 hours, followed by further drying under continuous stirring at the same temperature to yield paroxetine hydrochloride hernihydrate as a white crystalline solid.
Claims (20)
- Claims 1. A process for the preparation of paroxetine hydrochloride heniihydrate that is substantially free from discolouration, which comprises treating discoloured paroxetine hydrochloride hemihydrate with one or more of an acidic alumina or a 3M Zetacarbon®.
- 2. A process according to claim 1 comprising the preparation of paroxetine hydrochloride hemihydrate that is substantially free from discolouration, by treating the discoloured paroxetine hydrochloride hemihydrate with a 3M Zetacarbon®.
- 3. A process according to any one of claims 1 or 2 wherein the Zetacarbon® is selected from one or more of Zetacarbon® grade Rl 1SP, R12SP, R13SP, R14SP, R1SSP, R31SP, R32SP, R33SP, R34SP, R3SSP, RS1SP, RS2SP, RS3SP, R54SP and R5SSP.
- 4. A process according to any one of claims I to 3 wherein the Zetacarbon® is selected from one or more of Zetacarbon® grade R5 1SP, RS2SP, RS3SP, R54SP and RSSSP.
- 5. A process according to any one of claims 1 to 4 wherein the Zetacarbon® is Zetacarbon® grade R5SSP.
- 6. A process according to any one of the claims 1 to 5 wherein the Zetacarbon® comprises from 1 to 10 filter elements.
- 7. A process according to claim I comprising the preparation of paroxetine hydrochloride hemihydrate that is substantially free from discolouration, by treating the discoloured paroxetine hydrochloride hemihydrate with an acidic alumina.
- 8. A process according to claim 7 wherein the acidic alumina has a pH of 4.5±0.5.
- 9. A process according to any one of claims 7 or 8 wherein the acidic alumina comprises particles of from about 0.05 to about 0.15mm diameter.
- 10. A process according to any one of the preceding claims wherein the paroxetine hydrochloride hemihydrate is in solution.
- 11. A process according to any one of the preceding claims wherein the paroxetine hydrochloride hemihydrate is in an alcohol solution.
- 12. A process according to any one of the preceding claims wherein the paroxetine hydrochloride hemihydrate is in an aqueous alcohol solution.
- 13. A process according to any one of the preceding claims wherein the paroxetine hydrochloride hemihydrate is in an aqueous IPA solution.
- 14. A process according to any one of the preceding claims wherein the paroxetine hydrochloride hemihydrate is in an aqueous IMS solution.
- 15. A process according to any one of the preceding claims wherein the flow rate is from about 1 to about 50 L/min.
- 16. The use of an acidic alumina in a process for the preparation of paroxetine hydrochloride hemihydrate that is substantially free from discolouration.
- 17. The use of a 3M Zetacarbon® in a process for the preparation of paroxetine hydrochloride hemihydrate that is substantially free from discolouration.
- 18. Paroxetine hydrochloride hemihydrate wherein any discolouring agents have been substantially removed.
- 19. Paroxetine hydrochloride hemihydrate according to claim 18 wherein any paroxetine quinone adduct has been substantially removed
- 20. The process or use substantially as hereinbefore described with reference to the accompanying examples.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1108345.8A GB201108345D0 (en) | 2011-05-18 | 2011-05-18 | Process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB201208567D0 GB201208567D0 (en) | 2012-06-27 |
| GB2491023A true GB2491023A (en) | 2012-11-21 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GBGB1108345.8A Ceased GB201108345D0 (en) | 2011-05-18 | 2011-05-18 | Process |
| GB1208567.6A Withdrawn GB2491023A (en) | 2011-05-18 | 2012-05-16 | The preparation of paroxetine hydrochloride hemihydrate that is free from discolouration |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GBGB1108345.8A Ceased GB201108345D0 (en) | 2011-05-18 | 2011-05-18 | Process |
Country Status (1)
| Country | Link |
|---|---|
| GB (2) | GB201108345D0 (en) |
Citations (5)
| 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 |
| EP0812827A1 (en) * | 1996-06-13 | 1997-12-17 | SUMIKA FINE CHEMICALS Co., Ltd. | Piperidine derivative as intermediates for the preparation of paroxetine and process for their preparation |
| WO2002102382A1 (en) * | 2001-06-14 | 2002-12-27 | Teva Pharmaceutical Industries Ltd. | A PROCESS FOR PREPARING PAROXETINE HCl WHICH LIMITS FORMATION OF PINK COLORED COMPOUNDS |
| EP1555262A1 (en) * | 2002-09-19 | 2005-07-20 | Sumitomo Chemical Company, Limited | Methods of crystal precipitation |
| US20060041138A1 (en) * | 2002-09-19 | 2006-02-23 | Shigeya Yamazaki | Process for producing paroxetine hydrochloride hydrate |
-
2011
- 2011-05-18 GB GBGB1108345.8A patent/GB201108345D0/en not_active Ceased
-
2012
- 2012-05-16 GB GB1208567.6A patent/GB2491023A/en not_active Withdrawn
Patent Citations (5)
| 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 |
| EP0812827A1 (en) * | 1996-06-13 | 1997-12-17 | SUMIKA FINE CHEMICALS Co., Ltd. | Piperidine derivative as intermediates for the preparation of paroxetine and process for their preparation |
| WO2002102382A1 (en) * | 2001-06-14 | 2002-12-27 | Teva Pharmaceutical Industries Ltd. | A PROCESS FOR PREPARING PAROXETINE HCl WHICH LIMITS FORMATION OF PINK COLORED COMPOUNDS |
| EP1555262A1 (en) * | 2002-09-19 | 2005-07-20 | Sumitomo Chemical Company, Limited | Methods of crystal precipitation |
| US20060041138A1 (en) * | 2002-09-19 | 2006-02-23 | Shigeya Yamazaki | Process for producing paroxetine hydrochloride hydrate |
Non-Patent Citations (2)
| Title |
|---|
| "ACTIVATED ALUMINA", Sigma-Aldrich. Published 28 March 2010. Accessed 12 September 2012. * |
| "ALUMINA", Sigma-Aldrich. Published 12th September 1998. Accessed 12 September 2012. * |
Also Published As
| Publication number | Publication date |
|---|---|
| GB201108345D0 (en) | 2011-06-29 |
| GB201208567D0 (en) | 2012-06-27 |
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