EP1033986A1 - Formulations contenant de la paroxetine dissoute - Google Patents

Formulations contenant de la paroxetine dissoute

Info

Publication number
EP1033986A1
EP1033986A1 EP98954631A EP98954631A EP1033986A1 EP 1033986 A1 EP1033986 A1 EP 1033986A1 EP 98954631 A EP98954631 A EP 98954631A EP 98954631 A EP98954631 A EP 98954631A EP 1033986 A1 EP1033986 A1 EP 1033986A1
Authority
EP
European Patent Office
Prior art keywords
paroxetine
solid
carrier
capsule
capsules
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP98954631A
Other languages
German (de)
English (en)
Inventor
Ahmad;SmithKline Beecham Pharmaceuticals GHAZAWI
Graham Stanley;SmithKline Beecham Pharm. 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.)
Filing date
Publication date
Application filed by SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Publication of EP1033986A1 publication Critical patent/EP1033986A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • A61K9/4891—Coated capsules; Multilayered drug free capsule shells
    • 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
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular 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
    • 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
    • A61P25/22—Anxiolytics
    • 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 of a pharmaceutically active compound, and to the use of the formulations in therapy.
  • this invention is concerned with new formulations of the anti-depressant paroxetine.
  • P.aroxetine hydrochloride hemihydrate is described in EP-A-0223403 of Beecham Group and paroxetine hydrochloride anhydrate Forms A, B, C and D are described in WO 96/24595 of SmithKline Beecham pic. All solid oral dosage forms of paroxetine hydrochloride sold to date have been in the form of oral swallow tablets, containing the hemihydrate.
  • WO 95/104448 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.
  • the oral swallow capsule comprises a capsule shell containing paroxetine as the free base or a pharmaceutically acceptable salt or solvate thereof in solution in a carrier.
  • the carrier may be liquid or solid.
  • the present invention provides an oral swallow solid dosage form containing paroxetine dissolved in a solid, semi-solid or gel carrier.
  • Capsules and solid dosage forms of this invention may be coated to assist in administration of the active ingredient, for example using an enteric coating material to prevent release of paroxetine in the stomach, coatings to delay or control release of paroxetine and coatings of taste-masking agents.
  • an enteric coating material to prevent release of paroxetine in the stomach
  • coatings to delay or control release of paroxetine and coatings of taste-masking agents Alternatively such materials can be incorporated in the carrier to achieve the same effect.
  • the capsules or solid dosage forms of present invention use paroxetine hydrochloride in a form other than the hemihydrate, and are formulated under conditions such there is no detectable conversion to hemihydrate during the manufacturing process.
  • paroxetine hydrochloride anhydrate has a tendency to convert at least O 99/26625
  • Solubilising agents such as the polysorbates, the poloxamers, cyclodextrins, ionic and non-ionic surface active agents, for example Pluronic F60 and Sorbitan esters may also be used to enhance the solubility of paroxetine hydrochloride in solvents acceptable for capsule use but in which paroxetine is poorly soluble.
  • oral swallow capsule most suitably denotes a capsule having a maximum volume of 0.86 ml .
  • Preferred capsules according to the present invention have a maximum volume of about 0.45 ml and more especially may lie in the range 0.2 to 0.4 ml , although capsules as small as 0.14 ml are also provided by the invention.
  • Formulations based on a solubilising agent and oils/lipids are preferably formulated with at least one antioxidant to maintain stability of the solution on storage. If it desired to use the solutions for filling capsules then the compatibility of the solution with the capsule material must be investigated.
  • paroxetine hydrochloride to a solvent system tends to lower the pH by at least 1 unit, then in general solvent systems with a pH of below 3.5 are not preferred.
  • liquid and semi-solid 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, isopropyl myristate; solid interesterified semi-synthetic glycerides eg Suppocire, Witepsol; liquid interesterified semi-synthetic glycerides eg Mig
  • the paroxetine needs to be soluble in the polymer carrier or a solvent/cosolvent that is soluble in the polymer carrier to an extent that allows a sufficient concentration so that the selected tablet size and volume can contain the desired unit dose.
  • the solvent/cosolvent must be compatible with the polymer carrier material and physiologically acceptable for administration to a patient.
  • the solid solution/semi-solid systems presented in this invention can be coated with suitable polymer that can be used with melt granulation or hot melt coating such as Precirol ATO 5 (Glyceryl palmito stearate) for taste-masking paroxetine and/or enterically coated with methacrylic acid copolymer C (e.g. Eudragit L 30 D-55).
  • suitable polymer that can be used with melt granulation or hot melt coating
  • Precirol ATO 5 Glyceryl palmito stearate
  • methacrylic acid copolymer C e.g. Eudragit L 30 D-55
  • paroxetine is dissolved in a carrier, optionally assisted by a cosolvent, and filled into capsules.

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Organic Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

L'invention concerne des formulations pharmaceutiques de paroxétine dans lesquelles la paroxétine est en solution dans un véhicule solide, semi-solide ou liquide. On utilise ces solutions afin de remplir des gélules ou on prépare des formes galénique solides, telles que des comprimés ou des granules, à partir de solutions solides seules. Elle concerne également de nouvelles formulations liquides dans lesquelles on utilise un agent solubilisant afin solubiliser la paroxétine, soit dans des huiles, soit dans des lipides, ainsi que des procédés permettant d'éviter la conversion d'autres formes de paroxétine en son hémihydrate, par l'intermédiaire de véhicules anhydres ou hydrophobes.
EP98954631A 1997-11-21 1998-11-18 Formulations contenant de la paroxetine dissoute Withdrawn EP1033986A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB9724544 1997-11-21
GBGB9724544.3A GB9724544D0 (en) 1997-11-21 1997-11-21 Novel Formulation
PCT/GB1998/003471 WO1999026625A1 (fr) 1997-11-21 1998-11-18 Formulations contenant de la paroxetine dissoute

Publications (1)

Publication Number Publication Date
EP1033986A1 true EP1033986A1 (fr) 2000-09-13

Family

ID=10822374

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98954631A Withdrawn EP1033986A1 (fr) 1997-11-21 1998-11-18 Formulations contenant de la paroxetine dissoute

Country Status (24)

Country Link
EP (1) EP1033986A1 (fr)
JP (1) JP2001523718A (fr)
KR (1) KR20010032320A (fr)
CN (1) CN1279608A (fr)
AP (1) AP2000001821A0 (fr)
AR (1) AR015485A1 (fr)
AU (1) AU1168099A (fr)
BG (1) BG104527A (fr)
BR (1) BR9814220A (fr)
CO (1) CO4970832A1 (fr)
DZ (1) DZ2658A1 (fr)
EA (1) EA200000552A1 (fr)
GB (1) GB9724544D0 (fr)
HU (1) HUP0100580A3 (fr)
IL (1) IL136106A0 (fr)
MA (1) MA24704A1 (fr)
NO (1) NO20002590L (fr)
OA (1) OA11385A (fr)
PE (1) PE20000381A1 (fr)
PL (1) PL340555A1 (fr)
SK (1) SK7342000A3 (fr)
TR (1) TR200001423T2 (fr)
WO (1) WO1999026625A1 (fr)
ZA (1) ZA9810637B (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9810180D0 (en) * 1998-05-13 1998-07-08 Smithkline Beecham Plc Novel formulation
EP1161241B1 (fr) * 1999-03-12 2005-12-07 Aesica Pharmaceuticals Ltd. Forme galenique pharmaceutique stable pour anhydrate de paroxetine
ES2206254T3 (es) 1999-07-01 2004-05-16 Italfarmaco S.P.A. Complejos de paroxetina con ciclodextrinas o derivados de ciclodextrinas.
DE19930454A1 (de) * 1999-07-02 2001-01-04 Knoll Ag Feste Paroxetin enthaltende Zubereitungen
US6720003B2 (en) 2001-02-16 2004-04-13 Andrx Corporation Serotonin reuptake inhibitor formulations
EP1455763B1 (fr) * 2001-12-21 2007-10-03 Supernus Pharmaceuticals, Inc. Formulation de gelule a administration orale presentant une stabilite physique accrue
SE0200475D0 (sv) * 2002-02-15 2002-02-15 Ltp Lipid Technologies Provide Oral farmaceutisk beredning
WO2006119779A2 (fr) * 2005-05-10 2006-11-16 Lifecycle Pharma A/S Composition pharmaceutique comprenant un antagoniste de l'aldosterone
JP2013512948A (ja) * 2009-12-08 2013-04-18 イル・ファ・カンパニー・リミテッド ２０−Ｏ−β−Ｄ−グルコピラノシル−２０（Ｓ）−プロトパナキサジオールを含む固体分散体
GB201020032D0 (en) * 2010-11-25 2011-01-12 Sigmoid Pharma Ltd Composition
CN103961333B (zh) * 2014-05-07 2020-02-21 浙江华海药业股份有限公司 甲磺酸帕罗西汀胶囊及其制备方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2216934A1 (fr) * 1995-04-03 1996-10-10 Abbott Laboratories Melanges homogenes de medicaments fondant a basse temperature et d'additifs, destines a une liberation lente
EA002034B1 (ru) * 1997-01-15 2001-12-24 Смитклайн Бичам Плс Композиция на основе пароксетина

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9926625A1 *

Also Published As

Publication number Publication date
DZ2658A1 (fr) 2003-03-22
KR20010032320A (ko) 2001-04-16
EA200000552A1 (ru) 2000-10-30
TR200001423T2 (tr) 2000-10-23
MA24704A1 (fr) 1999-07-01
SK7342000A3 (en) 2000-12-11
PE20000381A1 (es) 2000-05-07
AU1168099A (en) 1999-06-15
CN1279608A (zh) 2001-01-10
NO20002590L (no) 2000-07-19
BR9814220A (pt) 2001-12-26
AP2000001821A0 (en) 2000-06-30
BG104527A (en) 2001-04-30
IL136106A0 (en) 2001-05-20
HUP0100580A2 (hu) 2002-04-29
GB9724544D0 (en) 1998-01-21
JP2001523718A (ja) 2001-11-27
HUP0100580A3 (en) 2002-05-28
OA11385A (en) 2004-01-27
CO4970832A1 (es) 2000-11-07
AR015485A1 (es) 2001-05-02
PL340555A1 (en) 2001-02-12
WO1999026625A1 (fr) 1999-06-03
ZA9810637B (en) 2000-05-22
NO20002590D0 (no) 2000-05-19

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