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

Applications Claiming Priority (3)

Publications (1)

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• 1997
  • 1997-11-21 GB GBGB9724544.3A patent/GB9724544D0/en not_active Ceased
• 1998
  • 1998-11-18 TR TR2000/01423T patent/TR200001423T2/xx unknown
  • 1998-11-18 CN CN98811404A patent/CN1279608A/zh active Pending
  • 1998-11-18 DZ DZ980268A patent/DZ2658A1/xx active
  • 1998-11-18 WO PCT/GB1998/003471 patent/WO1999026625A1/en not_active Application Discontinuation
  • 1998-11-18 AU AU11680/99A patent/AU1168099A/en not_active Abandoned
  • 1998-11-18 AP APAP/P/2000/001821A patent/AP2000001821A0/en unknown
  • 1998-11-18 PE PE1998001126A patent/PE20000381A1/es not_active Application Discontinuation
  • 1998-11-18 PL PL98340555A patent/PL340555A1/xx unknown
  • 1998-11-18 KR KR1020007005532A patent/KR20010032320A/ko not_active Application Discontinuation
  • 1998-11-18 JP JP2000521827A patent/JP2001523718A/ja active Pending
  • 1998-11-18 BR BR9814220-8A patent/BR9814220A/pt not_active Application Discontinuation
  • 1998-11-18 SK SK734-2000A patent/SK7342000A3/sk unknown
  • 1998-11-18 IL IL13610698A patent/IL136106A0/xx unknown
  • 1998-11-18 HU HU0100580A patent/HUP0100580A3/hu unknown
  • 1998-11-18 EA EA200000552A patent/EA200000552A1/ru unknown
  • 1998-11-18 EP EP98954631A patent/EP1033986A1/en not_active Withdrawn
  • 1998-11-19 MA MA25357A patent/MA24704A1/fr unknown
  • 1998-11-19 AR ARP980105880A patent/AR015485A1/es unknown
  • 1998-11-20 ZA ZA9810637A patent/ZA9810637B/xx unknown
  • 1998-11-20 CO CO98068459A patent/CO4970832A1/es unknown
• 2000
  • 2000-05-19 NO NO20002590A patent/NO20002590L/no not_active Application Discontinuation
  • 2000-05-19 OA OA1200000153A patent/OA11385A/en unknown
  • 2000-06-13 BG BG104527A patent/BG104527A/xx unknown

Non-Patent Citations (1)

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