MXPA00009137A - Crystalline form of paroxetine - Google Patents
Crystalline form of paroxetineInfo
- Publication number
- MXPA00009137A MXPA00009137A MXPA/A/2000/009137A MXPA00009137A MXPA00009137A MX PA00009137 A MXPA00009137 A MX PA00009137A MX PA00009137 A MXPA00009137 A MX PA00009137A MX PA00009137 A MXPA00009137 A MX PA00009137A
- Authority
- MX
- Mexico
- Prior art keywords
- paroxetine
- free base
- crystalline
- product
- solution
- Prior art date
Links
- 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 description 47
- 229960002296 paroxetine Drugs 0.000 title claims abstract description 42
- 239000012458 free base Substances 0.000 claims abstract description 39
- 239000002904 solvent Substances 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 4
- 238000002329 infrared spectrum Methods 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 206010012378 Depression Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 239000000047 product Substances 0.000 description 25
- 239000000243 solution Substances 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- 239000003921 oil Substances 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L mgso4 Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N n-heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 229960005183 Paroxetine Hydrochloride Drugs 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000005712 crystallization Effects 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- RQBJOWKBGCDPOS-RVXRQPKJSA-N acetic acid;(3S,4R)-3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidine Chemical compound CC(O)=O.C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 RQBJOWKBGCDPOS-RVXRQPKJSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000008079 hexane Substances 0.000 description 3
- 201000008430 obsessive-compulsive disease Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 230000000069 prophylaxis Effects 0.000 description 3
- SHIJTGJXUHTGGZ-RVXRQPKJSA-N (3S,4R)-3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidin-1-ium;methanesulfonate Chemical compound CS(O)(=O)=O.C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 SHIJTGJXUHTGGZ-RVXRQPKJSA-N 0.000 description 2
- 229960002567 Paroxetine mesylate Drugs 0.000 description 2
- 206010036618 Premenstrual syndrome Diseases 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000001225 therapeutic Effects 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 1
- 206010001897 Alzheimer's disease Diseases 0.000 description 1
- 206010002855 Anxiety Diseases 0.000 description 1
- 206010057666 Anxiety disease Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 229910016523 CuKa Inorganic materials 0.000 description 1
- 206010061428 Decreased appetite Diseases 0.000 description 1
- 206010013982 Dysthymic disease Diseases 0.000 description 1
- 241000406221 Hypostomus robinii Species 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 206010027599 Migraine Diseases 0.000 description 1
- 208000008085 Migraine Disorders Diseases 0.000 description 1
- 210000004940 Nucleus Anatomy 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010033666 Panic disease Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 230000001430 anti-depressive Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 238000005102 attenuated total reflection Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L na2so4 Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- -1 paroxetine compound Chemical class 0.000 description 1
- 229920000314 poly p-methyl styrene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 201000009032 substance abuse Diseases 0.000 description 1
- 231100000736 substance abuse Toxicity 0.000 description 1
Abstract
Pure, solvent-free, for example crystalline, paroxetine free base;and its use in therapy to treat depression.
Description
PAROXETINE CRYSTALLINE FORM
DESCRIPTIVE MEMORY
The present invention relates to novel pharmaceutically active compounds and, in particular, to novel crystalline forms of paroxetine. Pharmaceuticals with antidepressant and anti-Parkinson properties are described in US-A-3912743 and US-A-4007196. An especially important compound among those described is paroxetine, the (-) trans isomer of 4- (4'-fluorophenyl) -3- (3 ', 4'-methylenedioxy-phenoxymethyl) -piperidine. In the literature, this compound is isolated as an acid salt, especially the hydrochloride. Paroxetine is approved for human use as a hydrochloride salt and has been proposed for the treatment and prophylaxis of, among other conditions, depression, obsessive-compulsive disorder (OCD) and panic. Paroxetine hydrochloride has been described in the literature as a crystalline hemihydrate (see EP-A-0223403 by Beecham Group) and as various forms of crystalline anhydrate (see WO96 / 24595 by SmithKine Beecham). The paroxetine free base has hitherto been described in the literature only as an oil and, therefore, the free base has not been considered in itself for therapeutic use, with preference being given to crystalline forms that can be purified and processed more easily in dosed forms. The present invention provides the free base of paroxetine in crystalline form and the use of the free base of crystalline paroxetine as a therapeutic agent. The free base of crystalline paroxetine is characterized by a narrow band in the infrared spectrum (cloud biter) at about 3330 cm "1, which is not present in the infrared spectrum of the liquid form. melting point in the range of 45 to 47 ° C. The free base of paroxetine can be prepared by crystallization from a solution in an organic solvent, such as propan-2-ol.Crystallization is an effective method to remove impurities and / or solvent.A further aspect of the invention therefore provides a paroxetine free base, which is substantially pure, for example, at least 98%, preferably at least 99%, most preferably at least 99.5% A further aspect of the invention provides a paroxetine free base, which is substantially free of solvent, for example, containing less than 2%, preferably less than 1%, most preferably less 0.5%, more preferably less than 0.1% solvent.
A suitable solution of the free base can be prepared by adding a base, such as triethylamine, to a solution of a crystalline paroxetine salt, especially the hydrochloride. Alternatively, the solution can be prepared by basifying a solution of an amorphous paroxetine hydrochloride or a crystalline anhydrate or a hydrated form of paroxetine hydrochloride. The preparation of the free base and the maleic acid salt are described in Example 2 of US Pat. 4007196. Acetate salt can also be used. EP-A-0223403 describes processes for forming suitable salts. Also, the paroxetine free base can be prepared in solution by adding a base, such as potassium hydroxide, to a solution of N-protected paroxetine compound, such as N-phenoxycarbonylparoxetine. The crystallization of the paroxetine free base from the solution can be initiated by customary means, such as the addition of a non-solvent, evaporation of solvent, cooling of a saturated solution, addition of nuclei or seeds or scraping the walls of the container containing a supersaturated solution of the free base or the free base in the form of an oil. Preferably, the crystallization is carried out using seeds of the crystalline paroxetine free base. The seeds can be prepared by routine methods from solutions as described above.
The products of this invention can be formulated for therapy, as described in EP-A-0223403 or WO96 / 00477 for the hydrochloride. The amount of paroxetine used is adjusted in such a way that in a single unit dose, there is a therapeutically effective amount of paroxetine. Preferably, the dose of one unit contains 10 to 100 mg of paroxetine (measured in terms of the free base). The most preferred amount of paroxetine in a dose of one unit is 10 mg, 20 mg, 30 mg, 40 mg or 50 mg. The amount of paroxetine that is most preferred at a dose of one unit is 20 mg. The therapeutic uses of the paroxetine product of this invention include the treatment of: alcoholism, anxiety, depression, obsessive-compulsive disorder, panic disorder, chronic pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia, premenstrual syndrome ( PMS), depression of adolescence, tricotilomania, dysthymia and substance abuse, which are referred to as 'disorders'. Accordingly, this invention also provides: a pharmaceutical composition for treatment or prophylaxis of disorders, which comprises a product according to the invention and a pharmaceutically acceptable carrier; the use of a product according to the invention to prepare a medicament for the treatment or prophylaxis of the disorders; and a method for treating disorders, which is the administration of an effective or prophylactic amount of a product according to the invention to a person suffering from one or more of the disorders. The invention is illustrated by the following examples:
EXAMPLE 1 Preparation of the crystalline paroxetine free base
Paroxetine hydrochloride (50 g) was dissolved in dichloromethane (250 ml) by adding triethylamine (67.6 g) and stirred at 20 ° C for 12 hours. Solid triethylamine hydrochloride was filtered and the filtrate was washed twice with water (2 x 200 ml), dried with anhydrous magnesium sulfate and evaporated to form a viscous oil, removing as much solvent as possible. Propan-2-ol (165 ml) was added and the mixture was heated and stirred to form a homogeneous solution. The solution was cooled to -10 ° C and the walls of the container were scraped to initiate seeding. After 12 hours, the product was filtered, washed with propan-2-ol (50 ml at -10 ° C) and dried under vacuum.
EXAMPLE 2
A paroxetine-free base solution (obtained from 80 g of paroxetine hydrochloride hemidohydrate) was evaporated in propan-2-ol under vacuum to remove the solvent. Approximately 13 g of residual oil were seeded with paroxetine free base crystals and allowed to stand for 18 hours, after which a crystalline white solid formed. Purity of CLAR 98.04% Propan-2-ol residual < 0.1% w / w Melting point 45-47 ° C IR data (nude mordant) cm "1
XRD data, CuKa radiation, scrutinized from 3.5 to 35 degrees.
Angle (degrees 2T) Relative intensity (%) 4.1 24.7 6.1 1.1 8.2 0.5 13.2 12.3 13.6 2.3 14.4 8.9 15.5 19.0 16.1 54.1 16.6 19.5 18.0 77.3 19.9 83.5 20.8 41.0 21.1 33.8 22.3 100.0 22.8 39.6 23.5 14.1 23.9 21.0 10 24.5 26.8 25.6 19.2 26.3 7.2 27.4 43.0 28.0 8.4 29.2 10.7 30.5 14.6 31.1 4.6 32.1 2.5 32.9 6.2 15 33.8 7.0
NMR data in solid state (ppm)
-160 wide 155.2 149.5 142.5 140.5 129.6 115.7 107.6 102.6 99.2 70.8 52.7 48.6 46.5 45.3 35.1
EXAMPLE 3
Paroxetine mesylate (10.0 g) was added to water (100 ml) and the
The mixture was stirred until a complete solution was observed. Ethyl acetate (100 ml) was added, followed by an aqueous solution of sodium hydroxide (10% by weight, 20 ml) and the two-phase mixture was stirred vigorously for 5 minutes. The layers were allowed to settle and the organic layer was separated
and washed with water (100 ml). The organic layer was separated, dried over magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to
water bath heated to 40 ° C, until no more solvent came out, to give a
pale orange-brown viscous oil.
The product was analyzed by 1 H NMR (CDCl 3) and found to be consistent with paroxetine free base containing ethyl acetate, 5.6% w / w. The free base of crystalline paroxetine was seeded in the viscous oil and allowed to stand at 21 ° C for 24 hours to obtain the free base of paroxetine as a crystalline solid. The product was dried under vacuum at 21 ° C for 6 hours. Product weight: 7.5 g. Ethyl acetate content: 0.8% w / w. The product was dried for a further 3 hours under vacuum at 21 ° C to obtain a paroxetine free base containing ethyl acetate, 0.2% w / w (by 1 H NMR). CLAR analysis: 98.7%.
EXAMPLE 4
An aqueous solution of sodium hydroxide (20% by weight, 20 ml) was added to a stirred suspension of paroxetine-propan-2-ol hydrochloride solvate (10.0 g) in a mixture of ethyl acetate (100 ml) and water (100 ml), and the mixture was stirred vigorously for 5 minutes. The layers were allowed to settle and the organic layer was separated and washed with water (100 ml). The organic layer was separated, dried over magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure in a water bath heated at 40 ° C for 30 minutes, when the removal of the solvent appeared to be complete, to obtain a viscous pale brown oil. The product was analyzed by 1 H NMR (CDCl 3) and found to be consistent with the paroxetine free base containing ethyl acetate, 5.5% w / w. The crystalline paroxetine free base was seeded into the product and allowed to stand at 21 ° C for 24 hours to give a pale brown crystalline solid. The product was dried under vacuum at 21 ° C for 6 hours. Product weight: 8.1 g. Ethyl acetate: 0.8% w / w (by 1 H NMR). The product was dried for a further 3 hours under vacuum at 21 ° C to obtain a paroxetine free base containing ethyl acetate, 0.2% w / w (by 1 H NMR).
EXAMPLE 5
Paroxetine acetate (10.0 g) was added to water (100 ml) and the mixture was stirred until a complete solution was observed. Ethyl acetate (100 ml) was added followed by an aqueous solution of sodium hydroxide (10% by weight, 20 ml) and the two-phase mixture was stirred vigorously for 5 minutes. The layers were allowed to settle and the organic layer was separated and washed with water (100 ml). The organic layer was dried over magnesium sulfate, filtered, and the filtrate was evaporated under reduced pressure in a water bath heated to 40 ° C, until the removal of the solvent appeared to be complete, to obtain a viscous, colorless oil. The product was analyzed by 1 H NMR (CDCl 3) and found to be consistent with paroxetine free base containing ethyl acetate, 5.9% w / w. The free base of crystalline paroxetine was seeded in the viscous oil and allowed to stand at 21 ° C for 24 hours. The product was dried under vacuum at 21 ° C for 6 hours. Product weight: 8.2 g. Ethyl acetate content: 0.8% w / w (1 H NMR). The product was dried for a further 3 hours under vacuum at 21 ° C to obtain a paroxetine free base containing ethyl acetate, 0.2% w / w (1 H NMR). CLAR analysis: 99.2%.
EXAMPLE 6
A mixture of paroxetine-free base (2.0 g) and heptane (50 ml) was stirred and heated to 55 ° C under a nitrogen atmosphere. The resulting clear solution was decanted to separate it from a small amount of insoluble residues and cooled to 21 ° C under a nitrogen atmosphere and stirred for a period of 30 minutes. The mixture was cooled to 0 ° C while stirring for 10 minutes, and the resulting white crystalline solid was collected by filtration and washed with cold heptans (5 ml at 0 ° C). The product was dried under vacuum at 21 ° C for 4 hours to obtain a paroxetine free base as a free flowing white crystalline solid. Product weight: 1.0 g. Heptane content: < 0.1% w / w (by 1 H NMR). CLAR analysis: 99.6%. IR (nude mordant): major bands at 3328, 3051, 2811, 1627, 1603, 1509, 1502, 1489, 1329, 1283, 1248, 1218, 1188, 1159, 1143, 1113, 1101, 1038, 1027, 976, 934, 919, 888, 849, 828, 801, 776, 760, 722, 652, 621, 592, 574, 542, 527, 490, 471, 458 cm "1. X-ray powder diffractogram: Peaks greater than:
Angle (degrees 2 teta) Relative intensity (%) 4.1 53.6 8.2 1.5 12.4 2.0 13.2 10.1 14.5 7.2 15.5 7.4 16.1 39.2 16.7 13.7 18.1 64.5 19.9 4.34 20.3 22.4 20.9 37.1 21.2 20.4 22.4 100.0 22.9 17.8 23.5 4.6 24.0 17.7 24.7 13.0 25.7 26.2 26.0 8.6 26.4 6.4 27.5 50.2 28.4 6.3 29.2 18.2 30.5 17.0 31.1 8.0 31.7 7.7 32.1 6.7 33.0 8.6 33.9 9.9
EXAMPLE 7
A paroxetine-free base mixture (1.1 g) and hexane (25 ml) was stirred and heated to 55 ° C under a nitrogen atmosphere. The resulting clear solution was decanted to separate it from a small amount of insoluble residues and then cooled to -5 ° C while stirring under a nitrogen atmosphere. After stirring at -5 ° C for 10 minutes, a crystalline product was collected by filtration, washed with cold hexane (5 ml at -5 ° C) and dried under vacuum at 21 ° C for 4 hours to give as a result a paroxetine free base as a free-flowing white crystalline solid. Product weight: 0.52 g. Hexane content: < 0.1% (by 1 H NMR). CLAR analysis: 98.2%.
EXAMPLE 8
Paroxetine mesylate (3.0 g) was added to water (35 ml) and the mixture was stirred until a complete solution was observed. Ethyl acetate (35 ml) was added, followed by an aqueous solution of sodium hydroxide (10% by weight, 7.5 ml) and the two-phase mixture was stirred vigorously for 5 minutes. The layers were allowed to settle and the organic layer was separated and washed with water (35 ml). The organic layer was separated, dried over magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure in a water bath heated at 40 ° C for 30 minutes to obtain a pale orange-brown viscous oil. Heptane (55 ml) was added to the residue and the mixture was stirred and heated to 55 ° C under a nitrogen atmosphere. The resulting clear solution was decanted to separate it from a small amount of insoluble residues and then cooled to -5 ° C while stirring under a nitrogen atmosphere. After stirring at -5 ° C for 10 minutes, a crystalline product was collected by filtration, washed with cold heptane (10 ml at -5 ° C) and dried under vacuum at 21 ° C for 4 hours to obtain a paroxetine base as a free flowing white crystalline solid. Product weight: 1.1g. Heptane content: <0.1% w / w (by 1 H NMR). No ethyl acetate was observed by 1 H NMR: HPLC analysis: 99.2%.
EXAMPLE 9
A conical flask equipped with a magnetic stir bar was charged with paroxetine acetate (40.4 g), water (400 ml) and ethyl acetate (300 ml). The mixture was stirred until all the paroxetine acetate had dissolved and then 60 grams of an aqueous solution of sodium hydroxide (10% by weight) was added. The suspension was stirred for an additional 30 minutes. The resulting layers were separated and the aqueous layer was extracted with ethyl acetate (1 x 100 ml). The combined organic layers were washed with water (2 x 200 ml), dried over sodium sulfate and concentrated by evaporation under reduced pressure to obtain an oil, which, upon standing, crystallized slowly to produce a base of water. crystalline paroxetine. Performance = 32.9 g IR (Attenuated total reflection): 3331, 1628, 1605, 1500, 1488, 1466, 1439, 1395, 1329, 1283, 1246, 1219, 1185, 1159, 1143, 1113, 1102, 1036, 1027, 1015 , 976, 947, 934, 920, 889, 848, 827, 815, 801, 776, 760, 722, 652, 621,592, 572 cm "1.
Claims (7)
1. - A free base of paroxetine in crystalline form. 2.- A crystalline paroxetine-free base, further characterized by a narrow band in the infrared spectrum (nuxant mordant) at approximately 3330 cm. "1 .- A free base of paroxetine in a substantially pure form. free base of paroxetine which is substantially free of solvents 5. A pharmaceutical composition comprising a product according to any of claims 1 to 4 and a pharmaceutically acceptable carrier 6.- The use of a product in accordance with any of Claims 1 to 4 for preparing a medicament or for the treatment of depression 7. A process for preparing a product according to any of claims 1 to 4, which consists of crystallizing a paroxetine-free base from a oil or a solution.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9817115.0 | 1998-08-06 | ||
GB9805581.7 | 1998-08-06 | ||
GB9813054.5 | 1998-08-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA00009137A true MXPA00009137A (en) | 2001-07-09 |
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