MXPA99006594A - Paroxetine compositions - Google Patents
Paroxetine compositionsInfo
- Publication number
- MXPA99006594A MXPA99006594A MXPA/A/1999/006594A MX9906594A MXPA99006594A MX PA99006594 A MXPA99006594 A MX PA99006594A MX 9906594 A MX9906594 A MX 9906594A MX PA99006594 A MXPA99006594 A MX PA99006594A
- Authority
- MX
- Mexico
- Prior art keywords
- paroxetine hydrochloride
- spray
- paroxetine
- dried
- process according
- Prior art date
Links
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 title claims abstract description 70
- 239000000203 mixture Substances 0.000 title claims abstract description 14
- 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 7
- 229960002296 paroxetine Drugs 0.000 title claims abstract description 7
- 229960005183 paroxetine hydrochloride Drugs 0.000 claims abstract description 32
- 239000000243 solution Substances 0.000 claims abstract description 9
- 238000001694 spray drying Methods 0.000 claims abstract description 9
- 239000007787 solid Substances 0.000 claims abstract description 7
- 239000007864 aqueous solution Substances 0.000 claims abstract description 5
- 239000012453 solvate Substances 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 208000035475 disorder Diseases 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 4
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 208000007848 Alcoholism Diseases 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 208000032841 Bulimia Diseases 0.000 claims description 2
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 2
- 208000000094 Chronic Pain Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 208000002193 Pain Diseases 0.000 claims description 2
- 206010039966 Senile dementia Diseases 0.000 claims description 2
- 206010041250 Social phobia Diseases 0.000 claims description 2
- 201000007930 alcohol dependence Diseases 0.000 claims description 2
- 208000022531 anorexia Diseases 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 206010061428 decreased appetite Diseases 0.000 claims description 2
- 208000024732 dysthymic disease Diseases 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 208000019906 panic disease Diseases 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 201000009032 substance abuse Diseases 0.000 claims description 2
- 231100000736 substance abuse Toxicity 0.000 claims description 2
- 208000011117 substance-related disease Diseases 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 208000002271 trichotillomania Diseases 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 238000009472 formulation Methods 0.000 abstract description 6
- 239000002245 particle Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- BPSNETAIJADFTO-UHFFFAOYSA-N 2-pyridinylacetic acid Chemical compound OC(=O)CC1=CC=CC=N1 BPSNETAIJADFTO-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 241000907788 Cordia gerascanthus Species 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Abstract
Paroxetine hydrochloride is obtained in a free-flowing and easily soluble form (suitable for preparing solid formulations or aqueous solutions, suitable for parenteral use) by spray-drying solutions of paroxetine hydrochloride hemihydrate or other anhydrate/hydrate/solvate/amorphous forms.
Description
i PAROXETINE COMPOSITIONS
DESCRIPTIVE MEMORY
The present invention relates to a process for the preparation of a pharmaceutically active compound and to the use of said compound prepared in therapy. In particular, this invention relates to the preparation of a paroxetine hydrochloride in a free-flowing form. Pharmaceuticals with antidepressant and anti-Parkinson properties are described in documents EUA-A-3912743 and EUA-A-4007196. An especially important compound among those that are exposed in paroxetine is the (-) trans isomer 4- (4'-fluorophenyl) -3 ', 4'-methylenedioxy-phenoxymethyl) -piperidine. This compound is used in therapy as the hydrochloride salt to treat, among others, depression, obsessive-compulsive disorder (OCD) and panic. Paroxetine hydrochloride is described in the books as a crystalline hemihydrate (see EP-A-0223403 of the Beecham Group) and as various forms of crystalline anhydrate (see WO96 / 24595 or SmithKine Beecham foot). These known forms contain properties that are not ideal for all pharmaceutical applications, and are prepared by means of multistep procedures involving precipitation under carefully controlled conditions, filtration, drying and homogenization. Preferred crystallization methods use organic solvents which, when compared to water, are expensive and are associated with safety and environmental problems. In addition, the difficulty to produce crystalline products with uniform and regular particle size causes problems for their formulation by encapsulation. Also, the flow characteristics of the crystalline products limit the mass transfer option and the formulation technologies that can be used, while dust formation and electrostatic properties can be dangerous. Also, commercially known forms of paroxetine hydrochloride are relatively insoluble and slow to dissolve completely. There remains a need to find a paroxetine hydrochloride with improved processing and formulation characteristics. According to the first aspect of the invention, there is a process for preparing a paroxetine hydrochloride in a free-flowing form containing a spray-dried paroxetine hydrochloride solution. The supply material for spray drying can be conveniently prepared, for example, by dissolving paroxetine-free base in aqueous hydrochloric acid, although other solid forms of paroxetine hydrochloride can also be dissolved. For example, the supply material can be prepared by dissolving amorphous paroxetine hydrochloride or an anhydrate, hydrate or crystalline paroxetine hydrochloride solvate in a suitable solvent. The solvent used can be pure water or a mixture of water with compatible organic solvents. Suitable compatible organic solvents include pyridine-acetic acid, acetonitrile, acetone, ethanol, propan-1-ol, butan-1-ol and tetrahydrofuran. Alternatively, a suitable organic solvent can be used alone to form a solution with paroxetine hydrochloride. It is also possible to use heating to reach and maintain the complete solution, since once dissolved and in the absence of seeds in a crystalline form, the aqueous solutions are stable at room temperature for several days. Suitable concentrations of paroxetine hydrochloride subjected to spray drying range from 1 to 30% by weight, preferably from 5% to 20% by weight. The use of conventional spray drying procedures under normal conditions generally results in sticky paroxetine hydrochloride particles adhering to and between the sides of the apparatus. However, when the apparatus and operating conditions are selected to ensure that the particles are sufficiently cold before reaching the walls of the apparatus, successful spray drying can be carried out. It is necessary to have careful control of the size of the drop in the nozzles of the sprinkler, proportions of air flow and temperatures to adapt the device used. The paroxetine product of the previous procedure is free-flowing, moist and dissolves quickly; Solutions with high concentrations can be prepared without resorting to heating. According to the above, a second aspect of this invention is spray dried paroxetine hydrochloride.
It has been found that the spray-dried paroxetine hydrochloride of this invention is particularly suitable for applications where uniform particle size and good flow properties are of great advantage. In addition, as a result of the control of the possible particle size through spray drying, the product can be handled conveniently and safely without the hazards associated with the powder produced when preparing paroxetine hydrochloride solids. Examples of applications where the particle size is uniform are advantageous and include controlled release and microencapsulation (particle coating technology). It is possible to produce samples with different particle sizes for specific applications, for example in the 10-1000 micron scale. The microencapsulation can be incorporated into the spray drying process or can be carried out in a subsequent step. This technology is useful for masking the taste, releasing fast or controlled formulations, as well as controlling the pharmacokinetics including the parity of pharmacokinetic properties for the combination products. Isolation of the solid product from the solution of the supply material is possible in a single processing stage; so there is usually no need to mix, granulate, or dry, although it is possible to add an extra drying step if required. If aqueous supply materials are used, the costs and environmental problems normally associated with organic solvents are completely avoided. The spray-dried product of this invention can be formulated for therapy in the dosage forms described in EP-A-0223403 or WO96 / 24595. The free-flowing properties have advantages for the preparation of solid formulations. In addition, the readily soluble nature of the spray-dried paroxetine hydrochloride makes the preparation of solutions for parenteral use suitable. 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 in adolescents, trichotillomania, dysthymia and substance abuse, referred to below as "the disorders". In accordance with the foregoing, the present invention also relates to: a pharmaceutical composition for the treatment or prophylaxis of disorders, which contains spray-dried paroxetine hydrochloride and a pharmaceutically acceptable carrier or a reconstituted aqueous solution of dried paroxetine hydrochloride aspersion. the use of spray-dried paroxetine hydrochloride to manufacture a drug in the form of reconstituted solid or liquid for the treatment or prophylaxis of the disorders; and a method for treating disorders consisting of administering an effective or prophylactic amount of spray-dried paroxetine hydrochloride as a solid oral composition or a reconstituted aqueous parenteral or oral composition, to a person suffering from one or more of the disorders. The invention is illustrated by the following example.
EXAMPLE:
A 10% aqueous solution of paroxetine hydrochloride is spray-dried under the following conditions:
Niro Fielder Mobile Minor device Temperature setting of 185 ° C input Current inlet temperature 184-185 ° C Output temperature: 94-95 ° C Atomizer speed 40,000-50,000 rpm Pump speed 32-34 rpm (peristaltic) Air supply 4.8-5.2 barias DP through filters: Start of the passage of 57 mm of water Bag filter End of the 65 mm water passage Hepa filter Start of the 7 mm water passage DP through the holes of the End of the passage of 7 mm of water plate: Start of the passage of 80+ mm of water End of the passage of 80+ mm of water
Claims (11)
1. A process for preparing a free flow form of paroxetine hydrochloride which consists of spray drying a solution of paroxetine hydrochloride.
2. A process according to claim 1, wherein the supply material for spray drying is prepared by dissolving the free base of paroxetine in aqueous hydrochloric acid.
3. A process according to claim 1, wherein the supply material is prepared by dissolving an amorphous paroxetine hydrochloride or an anhydrate, hydrate or crystalline paroxetine hydrochloride solvate in a suitable solvent.
4. A method according to claims 1, 2 or 3, in which the solvent is pure water or a mixture of water with one or more compatible organic solvents.
5. A process according to claim 1 or 3, in which the paroxetine hydrochloride solution is in a suitable organic solvent, in the absence of water.
6. A process according to claim 4 or 5, in which the organic solvent is selected from pyridine, acetic acid, acetonitrile, acetone, ethanol, propan-1-ol, butan-1-ol or tetrahydrofuran.
7. - A method according to any of the preceding claims, wherein the concentration of paroxetine hydrochloride ranges from 5% to 20% by weight.
8. Sprinkle-dried paroxetine hydrochloride, obtained from the process of any of claims 1 to 7.
9. A pharmaceutical composition for the treatment or prophylaxis of disorders containing spray-dried paroxetine hydrochloride and a pharmaceutically vehicle. acceptable or an aqueous solution of reconstituted spray-dried paroxetine hydrochloride.
10. The use of spray-dried paroxetine hydrochloride to manufacture a medicament for the treatment or prophylaxis of one or more selected disorders of alcoholism, anxiety, depression, obsessive-compulsive disorder, panic disorder, chronic pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia, premenstrual syndrome (PMS), depression in adolescents, trichotillomania, dysthymia and substance abuse in a person.
11. The use of claim 10, wherein the medicament can be administered as a solid oral composition or as a reconstituted oral or parenteral aqueous composition.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9700692.8 | 1997-01-15 | ||
| GB9714873.8 | 1997-07-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA99006594A true MXPA99006594A (en) | 2000-01-21 |
Family
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