EP1077685A2 - Novel formulation containing paroxetine - Google Patents

Novel formulation containing paroxetine

Info

Publication number: EP1077685A2
Authority: EP; European Patent Office
Prior art keywords: paroxetine hydrochloride; hemihydrate; paroxetine; anhydrous; excipients
Prior art date: 1998-05-13
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 Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

EP99922303A

Other languages

German (de)

English (en)

French (fr)

Inventor

David P. SmithKline Beecham Pharma. ELDER

Graham S. SmithKline Beecham Pharma. LEONARD

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

SmithKline Beecham Ltd

Original Assignee

SmithKline Beecham Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-05-13

Filing date

1999-05-13

Publication date

2001-02-28

1999-05-13 Application filed by SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd

2001-02-28 Publication of EP1077685A2 publication Critical patent/EP1077685A2/en

Status Withdrawn legal-status Critical Current

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 80
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 description 16
229960002296 paroxetine Drugs 0.000 title description 16
239000000203 mixture Substances 0.000 title description 10
238000009472 formulation Methods 0.000 title description 9
229960005183 paroxetine hydrochloride Drugs 0.000 claims abstract description 32
239000002775 capsule Substances 0.000 claims abstract description 28
238000006243 chemical reaction Methods 0.000 claims abstract description 7
238000004519 manufacturing process Methods 0.000 claims abstract description 5
238000000034 method Methods 0.000 claims description 21
239000000546 pharmaceutical excipient Substances 0.000 claims description 11
125000005456 glyceride group Chemical group 0.000 claims description 10
238000007907 direct compression Methods 0.000 claims description 8
239000000463 material Substances 0.000 claims description 8
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 6
-1 monosaccharide sugars Chemical class 0.000 claims description 6
239000010773 plant oil Substances 0.000 claims description 6
239000007787 solid Substances 0.000 claims description 5
235000000346 sugar Nutrition 0.000 claims description 5
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 4
239000001913 cellulose Substances 0.000 claims description 4
239000007788 liquid Substances 0.000 claims description 4
239000002274 desiccant Substances 0.000 claims description 3
150000002191 fatty alcohols Chemical class 0.000 claims description 3
230000002209 hydrophobic effect Effects 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
229920000881 Modified starch Polymers 0.000 claims description 2
229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
150000001408 amides Chemical class 0.000 claims description 2
235000014113 dietary fatty acids Nutrition 0.000 claims description 2
150000002148 esters Chemical class 0.000 claims description 2
239000000194 fatty acid Substances 0.000 claims description 2
229930195729 fatty acid Natural products 0.000 claims description 2
150000004665 fatty acids Chemical class 0.000 claims description 2
150000002334 glycols Chemical class 0.000 claims description 2
239000008101 lactose Substances 0.000 claims description 2
229920003124 powdered cellulose Polymers 0.000 claims description 2
235000019814 powdered cellulose Nutrition 0.000 claims description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
239000007903 gelatin capsule Substances 0.000 description 7
235000019359 magnesium stearate Nutrition 0.000 description 7
239000000725 suspension Substances 0.000 description 7
OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 4
244000105624 Arachis hypogaea Species 0.000 description 3
GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 3
150000001875 compounds Chemical class 0.000 description 3
VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 3
239000000843 powder Substances 0.000 description 3
RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
235000017060 Arachis glabrata Nutrition 0.000 description 2
235000010777 Arachis hypogaea Nutrition 0.000 description 2
235000018262 Arachis monticola Nutrition 0.000 description 2
244000060011 Cocos nucifera Species 0.000 description 2
235000013162 Cocos nucifera Nutrition 0.000 description 2
229920000742 Cotton Polymers 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
244000068988 Glycine max Species 0.000 description 2
235000010469 Glycine max Nutrition 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
229960004977 anhydrous lactose Drugs 0.000 description 2
239000000935 antidepressant agent Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
238000007906 compression Methods 0.000 description 2
230000006835 compression Effects 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
239000012458 free base Substances 0.000 description 2
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
239000000832 lactitol Substances 0.000 description 2
235000010448 lactitol Nutrition 0.000 description 2
229960003451 lactitol Drugs 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
235000020232 peanut Nutrition 0.000 description 2
RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-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
HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
241001133760 Acoelorraphe Species 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
235000003911 Arachis Nutrition 0.000 description 1
208000032841 Bulimia Diseases 0.000 description 1
206010006550 Bulimia nervosa Diseases 0.000 description 1
208000020401 Depressive disease Diseases 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
239000004166 Lanolin Substances 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
208000008589 Obesity Diseases 0.000 description 1
208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
240000007817 Olea europaea Species 0.000 description 1
208000002193 Pain Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
206010036618 Premenstrual syndrome Diseases 0.000 description 1
235000004443 Ricinus communis Nutrition 0.000 description 1
206010039966 Senile dementia Diseases 0.000 description 1
206010041250 Social phobia Diseases 0.000 description 1
240000006474 Theobroma bicolor Species 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
208000022531 anorexia Diseases 0.000 description 1
230000001430 anti-depressive effect Effects 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
235000013871 bee wax Nutrition 0.000 description 1
239000012166 beeswax Substances 0.000 description 1
239000007963 capsule composition Substances 0.000 description 1
235000013869 carnauba wax Nutrition 0.000 description 1
239000004203 carnauba wax Substances 0.000 description 1
229960000541 cetyl alcohol Drugs 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
206010061428 decreased appetite Diseases 0.000 description 1
238000007908 dry granulation Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
UUXNRWQEPOCOIW-UHFFFAOYSA-N ethanol;octadecanamide Chemical compound CCO.CCCCCCCCCCCCCCCCCC(N)=O UUXNRWQEPOCOIW-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
229940100242 glycol stearate Drugs 0.000 description 1
229960001375 lactose Drugs 0.000 description 1
235000019388 lanolin Nutrition 0.000 description 1
229940039717 lanolin Drugs 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000059 polyethylene glycol stearate Polymers 0.000 description 1
201000000484 premenstrual tension Diseases 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000003908 quality control method Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000003860 storage Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1

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
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/485—Inorganic compounds
- 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

Definitions

the present invention relates to novel formulations and to the use of the formulations in the treatment and/or prevention of certain disorders.
This compound has been approved for human use and is marketed, in the form of its hydrochloride salt, in many countries around the world as an anti-depressant agent.
WO 95/16448 discloses that paroxetine is likely to develop a pink colour unless it is formulated into tablets using a formulation process in which water is absent, such as dry direct compression of paroxetine or dry granulation of paroxetine followed by compression into tablets.
dry was used to denote substantially dry as opposed to the wholesale addition of water which had been previously employed in the wet granulation process.
paroxetine hydrochloride in a form other than the hemihydrate, which is formulated into capsules under conditions such there is no detectable conversion to hemihydrate during the manufacturing process.
the paroxetine hydrochloride may, for example, be present in an amorphous form or as a crystalline anhydrate.
excipients which are essentially anhydrous for powder fill capsules that is to say, they contain less than 2%, more especially less than 1.5%, preferably less than 1% water
excipients which are essentially hydrophobic for solid or liquid filled capsules that is to say, they contain less than 2%, more especially less than 1.5%, preferably less than 1% water
dibasic calcium phosphate anhydrous and polyglycolized glycerides can be used to form oral swallow capsules with paroxetine hydrochloride anhydrate without undesired conversion to hemihydrate during the manufacturing process.
the capsules are then packaged with a desiccant in order to prevent conversion of anhydrate to hemihydrate on storage.
the present invention also provides a process for the preparation of paroxetine hydrochloride anhydrate capsules free of detectable hemihydrate which is characterised by the use of conditions such there is no detectable conversion of the anhydrate to hemihydrate during the manufacturing process.
Such conditions can be achieved by the use of essentially anhydrous/hydrophobic excipients under conditions of low relative humidity
excipients with the necessary low moisture content include materials such as dibasic calcium phosphate anhydrous, anhydrous direct compression lactose, monosaccharide sugars eg mannitol, disaccharide sugars eg lactitol, powdered cellulose, pregelatinised starch and similar materials. These materials may also be of a grade suitable for direct compression, as this can aid powder filling on the capsule filling machine and also impart appropriate compression characteristics on the blend as appropriate for certain types of capsule filling machines.
Dibasic calcium phosphate anhydrous is commercially available in a pharmaceutically acceptable grade, eg A-TAB (Rhone Poulenc) as the main excipient in a powder fill capsules formulation.
paroxetine hydrochloride anhydrate is mixed with dibasic calcium phosphate anhydrous and other pharmaceutically acceptable excipients such as a lubricant eg magnesium stearate and mixed in a suitable blender before filling cellulose capsule shells of intrinsically low moisture content (eg Shionogi Qualicaps. ⁇ 3%). Additionally, certain of the low
paroxetine hydrochloride anhydrate is mixed with direct compression lactilol and other pharmaceutically acceptable excipients such as a lubricant eg magnesium stearate and mixed in a suitable blender before filling cellulose capsule shells of intrinsically low- moisture content (eg Shionogi Qualicaps, ⁇ 3%).
excipients with the necessary hydrophobicity include materials such as polyglycolised glycerides eg Gelucire 44/14; complex fatty materials of plant origin eg theobroma oil. carnauba wax; plant oils eg peanut, olive, palm kernels, cotton. corn, soya; hydrogenated plant oils eg peanut, palm kernels, cotton, soya, castor. coconut; natural fatty materials of animal origin eg beeswax, lanolin, fatty alcohols eg cetyl. stearyl. lauric. myristic, palmitic, stearic; esters eg glycerol stearate, glycol stearate. ethyl oleate.
materials such as polyglycolised glycerides eg Gelucire 44/14; complex fatty materials of plant origin eg theobroma oil. carnauba wax; plant oils eg peanut, olive, palm kernels, cotton. corn,
paroxetine hydrochloride anhydrate is mixed with warm Lipex 101 in a suitable blender (to form a suspension) before filling into gelatin capsule shells.
a hydrogenated plant oil is commercially available in a pharmaceutically acceptable grade eg Lubritab (Edward Mendell).
a pharmaceutically acceptable grade eg Lubritab (Edward Mendell).
paroxetine hydrochloride anhydrate is mixed with molten Lubritab in a suitable blender, a hydrophilic excipent, for example anhydrous lactose is added (to form a suspension) before filling into gelatin capsule shells.
paroxetine hydrochloride anhydrate is mixed with molten Crodacol C95 in a suitable blender (to form a suspension) before filling into gelatin capsule shells.
a polyglycolised glyceride is commercially available in a pharmaceutically acceptable grade eg Gelucire 44/14 (Gattfosse).
paroxetine hydrochloride anhydrate is mixed with molten Gelucire 44/14 in a suitable blender (to form a solid suspension) before filling gelatin capsule shells.
a liquid interesterified semi-synthetic glycerides is commercially available in a pharmaceutically acceptable grade eg Labrafil M 2125CS (Gattfosse) or Miglyol 810/812 (Hull).
paroxetine hydrochloride anhydrate is mixed with Labrafil M 2125CS (Gatfosse) to produce a suspension in a hard or soft gelatin capsule formulation.
paroxetine hydrochloride anhydrate is mixed with Miglyol 810 (H ⁇ ls AG) in a suitable mixer to produce a suspension in a hard or soft gelatin capsule formulation.
a solid interesterified semi-synthetic glycerides is commercially available in a pharmaceutically acceptable grade eg Suppocire AM - DM (Gattfosse).
Suppocire AM - DM Geltfosse
paroxetine hydrochloride anhydrate is mixed with molten Suppocire DM in a suitable blender (to form a suspension) before filling into gelatin capsule shells.
the capsule formulation is packaged in standard pharmaceutical container/closure presentations, optionally with a desiccant.
the amount of paroxetine used is adjusted such that in a single unit dose there is a therapeutically effective amount of paroxetine.
the unit dose contains from
paroxetine 10 to 100 mg paroxetine (as measured in terms of the free base). More preferable the amount of paroxetine in a unit dose is lOmg, 20mg, 30mg. 40mg or 50mg. The most preferred amount of paroxetine in a unit dose is 20mg.
Paroxetine used in the formulation is in the form of the hydrochloride anhydrate which may be prepared according to the procedures outlined in WO 96/24595.
paroxetine has particular utility in the treatment of depression; paroxetine may also be used in the treatment of mixed anxiety and depression, obsessive compulsive disorders, panic, pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia and the depression arising from premenstrual tension and adolescence.
the present invention therefore also provides a method of treating or preventing any of the above disorders which comprises administering an effective or prophylactic amount of an oral swallow capsule prepared in accordance with the present invention.

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)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Inorganic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Medicinal Preparation (AREA)

EP99922303A 1998-05-13 1999-05-13 Novel formulation containing paroxetine Withdrawn EP1077685A2 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GBGB9810180.1A GB9810180D0 (en)	1998-05-13	1998-05-13	Novel formulation
GB9810180		1998-05-13
PCT/GB1999/001522 WO1999058116A2 (en)	1998-05-13	1999-05-13	Novel formulation containing paroxetine

Publications (1)

Publication Number	Publication Date
EP1077685A2 true EP1077685A2 (en)	2001-02-28

Family

ID=10831926

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
EP99922303A Withdrawn EP1077685A2 (en)	1998-05-13	1999-05-13	Novel formulation containing paroxetine

Country Status (20)

Country	Link
EP (1)	EP1077685A2 (id)
JP (1)	JP2002514593A (id)
KR (1)	KR20010043545A (id)
CN (1)	CN1309557A (id)
AP (1)	AP2000001985A0 (id)
AU (1)	AU3941099A (id)
BG (1)	BG105011A (id)
BR (1)	BR9910402A (id)
CA (1)	CA2331849A1 (id)
EA (1)	EA200001173A1 (id)
GB (1)	GB9810180D0 (id)
HU (1)	HUP0101931A3 (id)
ID (1)	ID27018A (id)
IL (1)	IL139596A0 (id)
NO (1)	NO20005681L (id)
PL (1)	PL344872A1 (id)
SK (1)	SK16972000A3 (id)
TR (1)	TR200003351T2 (id)
WO (1)	WO1999058116A2 (id)
ZA (1)	ZA200006465B (id)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE311883T1 (de)	1999-03-12	2005-12-15	Aesica Pharmaceuticals Ltd	Stabile pharmazeutische anwendungsform für paroxetin-anhydrat
HU226912B1 (en) *	2000-04-07	2010-03-01	Richter Gedeon Nyrt	New paroxetin salt and medicament containing it
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1998
- 1998-05-13 GB GBGB9810180.1A patent/GB9810180D0/en not_active Ceased
1999
- 1999-05-13 CA CA002331849A patent/CA2331849A1/en not_active Abandoned
- 1999-05-13 BR BR9910402-4A patent/BR9910402A/pt not_active Application Discontinuation
- 1999-05-13 KR KR1020007012660A patent/KR20010043545A/ko not_active Withdrawn
- 1999-05-13 SK SK1697-2000A patent/SK16972000A3/sk unknown
- 1999-05-13 WO PCT/GB1999/001522 patent/WO1999058116A2/en not_active Ceased
- 1999-05-13 IL IL13959699A patent/IL139596A0/xx unknown
- 1999-05-13 AP APAP/P/2000/001985A patent/AP2000001985A0/en unknown
- 1999-05-13 TR TR2000/03351T patent/TR200003351T2/xx unknown
- 1999-05-13 EP EP99922303A patent/EP1077685A2/en not_active Withdrawn
- 1999-05-13 EA EA200001173A patent/EA200001173A1/ru unknown
- 1999-05-13 CN CN99808548A patent/CN1309557A/zh active Pending
- 1999-05-13 JP JP2000547967A patent/JP2002514593A/ja active Pending
- 1999-05-13 PL PL99344872A patent/PL344872A1/xx unknown
- 1999-05-13 HU HU0101931A patent/HUP0101931A3/hu unknown
- 1999-05-13 AU AU39410/99A patent/AU3941099A/en not_active Abandoned
- 1999-05-13 ID IDW20002329A patent/ID27018A/id unknown
2000
- 2000-11-09 ZA ZA200006465A patent/ZA200006465B/en unknown
- 2000-11-10 NO NO20005681A patent/NO20005681L/no not_active Application Discontinuation
- 2000-11-30 BG BG105011A patent/BG105011A/xx unknown

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Also Published As

Publication number	Publication date
CA2331849A1 (en)	1999-11-18
ID27018A (id)	2001-02-22
HUP0101931A2 (hu)	2002-04-29
CN1309557A (zh)	2001-08-22
PL344872A1 (en)	2001-11-19
AU3941099A (en)	1999-11-29
WO1999058116A2 (en)	1999-11-18
HUP0101931A3 (en)	2002-10-28
SK16972000A3 (sk)	2001-06-11
BG105011A (en)	2001-07-31
GB9810180D0 (en)	1998-07-08
AP2000001985A0 (en)	2000-12-31
KR20010043545A (ko)	2001-05-25
NO20005681D0 (no)	2000-11-10
JP2002514593A (ja)	2002-05-21
EA200001173A1 (ru)	2001-04-23
BR9910402A (pt)	2001-01-09
TR200003351T2 (tr)	2001-03-21
NO20005681L (no)	2000-12-01
ZA200006465B (en)	2001-11-09
WO1999058116A3 (en)	2000-02-17
IL139596A0 (en)	2002-02-10

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US6524615B2 (en)	2003-02-25	Controlled release pharmaceutical composition
AU748396B2 (en)	2002-06-06	Composition
EP0697866A1 (en)	1996-02-28	High dose formulations
WO1999058116A2 (en)	1999-11-18	Novel formulation containing paroxetine
CA1150148A (en)	1983-07-19	Enterosoluble hard-capsulated medicaments
WO1999026625A1 (en)	1999-06-03	Formulations comprising dissolved paroxetine
AU2003224419A1 (en)	2003-09-09	Orally administrable pharmaceutical formulation
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MXPA00011153A (en)	2001-07-31	Novel formulation containing paroxetine
CZ20004185A3 (cs)	2001-05-16	Nový prostředek obsahující paroxetin
AU3940999A (en)	1999-11-29	Novel formulation containing paroxetine
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MXPA00011154A (en)	2001-12-04	Novel formulation containing paroxetine
CA2310407A1 (en)	1999-06-03	Formulations comprising dissolved paroxetine
MXPA00008849A (en)	2001-07-09	Composition
MXPA00005030A (en)	2001-05-07	Formulations comprising dissolved paroxetine