EP2010499A1 - Composition pharmaceutique d'oxcarbazepine à particules de 15 à 30 microns en moyenne - Google Patents

Composition pharmaceutique d'oxcarbazepine à particules de 15 à 30 microns en moyenne

Info

Publication number
EP2010499A1
EP2010499A1 EP07718769A EP07718769A EP2010499A1 EP 2010499 A1 EP2010499 A1 EP 2010499A1 EP 07718769 A EP07718769 A EP 07718769A EP 07718769 A EP07718769 A EP 07718769A EP 2010499 A1 EP2010499 A1 EP 2010499A1
Authority
EP
European Patent Office
Prior art keywords
oxcarbazepine
microns
value
tablet
film
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Withdrawn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
EP07718769A
Other languages
German (de)
English (en)
Other versions
EP2010499A4 (fr
Inventor
Brett Antony Mooney
Panagiotis Keramidas
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.)
Alphapharm Pty Ltd
Original Assignee
Alphapharm Pty 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
Priority claimed from AU2006902079A external-priority patent/AU2006902079A0/en
Application filed by Alphapharm Pty Ltd filed Critical Alphapharm Pty Ltd
Publication of EP2010499A1 publication Critical patent/EP2010499A1/fr
Publication of EP2010499A4 publication Critical patent/EP2010499A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
    • C07D223/22—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines
    • 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
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2893—Tablet coating processes

Definitions

  • compositions of oxcarbazepine with a median particle size of 15 to 30 microns
  • This invention relates to pharmaceutical compounds and compositions comprising oxcarbazepine.
  • Pharmaceutically active substances are commonly formulated into dosage forms to aid the delivery of small amounts thereof.
  • the amount of pharmaceutically active substance that will be present in oral dosage forms can vary from a very small amount such as about 0.125mg up to larger amounts such as about lOOOmg, depending on the pharmaceutically active substance being used and the pharmaceutical effective amount thereof.
  • the oral dosage form is often constituted of other pharmaceutically acceptable excipients that perform various functions depending on the dosage form and the mode of action required. These excipients have an effect on the method and rate of delivery of the pharmaceutically active substance to the patient.
  • Another aspect of pharmaceutical formulations that affects the rate of delivery or the bioavailability of the pharmaceutically active substance is the particle size thereof.
  • This relationship between particle size and bioavailability is well known in the pharmaceutical industry and across a range of pharmaceutical products.
  • studies into the effect of crystal size on the bioavailability of Benoxaprofen were conducted (Biomed Mass Spectrom., 1979 Apr, 6(4), pp 173-8, Wolen RL efc al ; J. Pharm. Sci . , 1979 JuI, 68(7), pp 850-2, Ridolfo AS et al) .
  • J. Pharm. Sci., 1980 Apr, 69(4), pp 391-4, Schoenwald RD & Stewart P disclose the effect of particle size on the ophthalmic bioavailability of dexamethasone stating that
  • WO 98/35681 (Novartis) further illustrates the effect of reducing the particle size of a drug with poor aqueous solubility.
  • the formulations disclosed therein comprise micronised oxcarbazepine particles with a median particle size of between 2 to 12 microns ( ⁇ m) . Such particle size enhances the dissolution rate and consequently the bioavailability.
  • the problem with micronised particles of such a small size is that the particles can agglomerate into larger particles, thereby reducing the solubility and consequently the bioavailability of the drug.
  • micronising to a small particle size can also lead to stability and/or discolouration problems. Additionally, micronisation to such a small particle size requires greater energy input, more time and greater controls on the micronisation process to achieve the required range whilst reducing the amount of rejected material.
  • US5472714 (Ciba-Geigy) discloses double-layered tablets with pigmented hydrophilic, permeable inner and outer coatings.
  • the pigments generally include amounts of iron oxide for colouration, so each coating layer may include iron oxide.
  • the Food and Drug Administration (US) has set limits for the maximum ingestion of iron oxide pigment to 5mg/day. Therefore, the amount of coating able to be used may be limited by the allowable amount of iron oxide that can be ingested per day to an amount which may be below that required to overcome any discolouration problem.
  • Bioavailability can also be increased with the use of a surfactant or wetting agent. This helps to increase the solubility of the pharmaceutically active substance and thus bioavailability. However, there can be an undesired interaction between the pharmaceutically active substance and the wetting agent. Therefore, it is not always beneficial to use a wetting agent to increase the solubility and/or bioavailability of a pharmaceutically active substance.
  • a pharma- ceutical composition comprising oxcarbazepine of a defined particle size overcomes the above problems with prior art.
  • oxcarbazepine having a D tV/0 . 5 ] value of between about 15 microns to about 30 microns and a D tV/0 . 9] value of less than or equal to 90 microns.
  • a pharmaceutical composition comprising oxcarbazepine wherein said oxcarbazepine has a particle size with a D [V/0 .
  • the composition is in the form of an oral dosage formulation, more preferably the oral dosage formulation is a tablet and in a particularly preferred embodiment the tablet is film-coated. Alternatively, the formulation is a capsule. Another advantage of a formu- lation according to the invention is that it need not be taken with food.
  • said oxcarbazepine has a particle size with a D[ V ,o. 5 ] of between about 18 microns and about 30 microns .
  • a tablet according to the invention comprising between about lOOmg to lOOOmg oxcarbazepine, typically lOOmg to 700mg.
  • the tablet comprises 150mg or alternatively 300mg or 600mg of oxcarbazepine.
  • a film-coated tablet composition comprising a core comprising between about 60 and 80% oxcarbazepine wherein said oxcarbazepine has a D [v , 0 . 5 ] value of between about 15 and 30 microns and a D[ V , 0 . 9 ] value of less than or equal to 90 microns, and pharmaceutically acceptable excipients .
  • the excipients include crospovidone, preferably between about 2 to 10%, hypromellose (hydroxy- propyl methylcellulose) , preferably between about 2 to 10%, microcrystalline cellulose, preferably between about 0 to 20%, colloidal anhydrous silica, preferably between about 0 to 5% and magnesium stearate preferably between about 0 to 5%.
  • the film-coated tablet composition comprises a core comprising about lOOmg to 700mg oxcarbazepine wherein said oxcarbazepine has a D [v , 0 . 5] value of between about 15 microns and about 30 microns and a Div,o.9] value of less than or equal to 90 microns and further comprising pharmaceutically acceptable excipients selected from crospovidone, preferably between about lOmg - 80mg, and more preferably 4 to 21mg hypromellose, preferably between about 5 to 50mg, and more preferably 4 to 21mg microcrystalline cellulose, preferably between about lOmg - lOOmg, and more preferably 0 to 40mg colloidal anhydrous silica, preferably between about 0 to llmg and magnesium stearate preferably between about 0 to llmg.
  • the film-coated tablet composition comprises a core comprising about 150mg of oxcarbazepine, wherein said oxcarbazepine has a D[ V ,0.5] value of between about 15 to 30 microns and a D[ V , o.s] value of less than or equal to 90 microns, and pharmaceutically acceptable excipients comprising 4 to 21mg of crospovidone, 4 to 21mg of hydroxypropyl methylcellulose, 0 to 42mg of microcrystalline cellulose, 0 to llmg of colloidal anhydrous silica and 0 to llmg of magnesium stearate.
  • the film-coated tablet composition comprises a core comprising about 300mg of oxcarbazepine, wherein said oxcarbazepine has a D[ V ,o. 5 ] value of between about 15 to 30 microns and a D [v , 0 . 9 ] value of less than or equal to 90 microns, and pharmaceutically acceptable excipients comprising 8 to 42mg of crospovidone, 8 to 42mg of hydroxypropyl methylcellulose, 0 to 84mg of microcrystalline cellulose, 0 to 22mg of colloidal anhydrous silica and 0 to 22mg of magnesium stearate.
  • the film-coated tablet composition comprises a core comprising about 600mg of oxcarbazepine, wherein said oxcarbazepine has a D[ V/0 . 5 ] value of between about 15 and microns and a D[ V/0 .9] value of less than or equal to 90 microns, and pharmaceutically acceptable excipients comprising 16 to 84mg of crospovidone, 16 to 84mg of hydroxypropyl methylcellulose, 0 to 168mg of microcrystalline cellulose, 0 to 44mg of colloidal anhydrous silica and 0 to 44mg of magnesium stearate.
  • a film-coated tablet according to the invention comprises one or more coating polymers preferably the or each coating polymer is selected from film-coating systems such as Opadry or Opadry II by Colorcon, preferably Opadry ® II Buff OY-LS-37200 and Opadry ® II White OY-LS-28908. In a particularly preferred embodiment, between about lmg to 20mg of the coating system is present.
  • the invention provides a method of treating partial seizures in patients with epilepsy comprising administering to a patient suffering from epilepsy an effective amount of oxcarbazepine or a pharmaceutical composition containing it, including a film-coated tablet, as described herein.
  • the present invention provides the use of oxcarbazepine or a pharmaceutical composition containing it, including a film-coated tablet, as described herein in the treatment of partial seizures in a patient with epilepsy.
  • the present invention provides the use of oxcarbazepine as described herein in the manufacture of a medicament for use in the treatment of partial seizures in a patient with epilepsy.
  • Figure 1 is a flow chart illustrating a process of preparing a pharmaceutical composition in accordance with the present invention. Detailed Description of the Preferred Embodiments
  • Table 1 - shows tablet formulations according to the invention.

Landscapes

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

Abstract

L'invention concerne l'Oxcarbazépine ayant une valeur D[v,0,5] allant de 15 microns à 30 microns et une valeur D[v,0,9] inférieure ou égale à 90 microns.
EP07718769A 2006-04-21 2007-04-20 Composition pharmaceutique d'oxcarbazepine à particules de 15 à 30 microns en moyenne Withdrawn EP2010499A4 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AU2006902079A AU2006902079A0 (en) 2006-04-21 Pharmaceutical compound and composition
PCT/AU2007/000522 WO2007121523A1 (fr) 2006-04-21 2007-04-20 Composition pharmaceutique d'oxcarbazépine À PARTICULES DE 15 À 30 microns EN moyenne

Publications (2)

Publication Number Publication Date
EP2010499A1 true EP2010499A1 (fr) 2009-01-07
EP2010499A4 EP2010499A4 (fr) 2012-07-18

Family

ID=38624464

Family Applications (1)

Application Number Title Priority Date Filing Date
EP07718769A Withdrawn EP2010499A4 (fr) 2006-04-21 2007-04-20 Composition pharmaceutique d'oxcarbazepine à particules de 15 à 30 microns en moyenne

Country Status (3)

Country Link
EP (1) EP2010499A4 (fr)
AU (1) AU2007242062A1 (fr)
WO (1) WO2007121523A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2029118A2 (fr) * 2006-01-31 2009-03-04 Teva Pharmaceutical Industries, Inc. Formulation pharmaceutique d'oxcarbazepine, et sa méthode de fabrication, caractérisée en ce que l'oxcarbazepine a une distribution de la taille des particules qui est large et multi-modale
ES2761265T3 (es) * 2013-03-15 2020-05-19 Aprecia Pharmaceuticals LLC Forma de dosificación de oxcarbazepina rápidamente dispersable
WO2015063670A1 (fr) * 2013-10-30 2015-05-07 Wockhardt Limited Composition orale solide a liberation modifiee comprenant de l'oxcarbazepine ou un sel pharmaceutiquement acceptable de ce compose

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998035681A1 (fr) * 1997-02-14 1998-08-20 Novartis Ag Comprimes d'oxacarbazepine enrobes par pelliculage
WO2002094774A2 (fr) * 2001-05-18 2002-11-28 Ranbaxy Laboratories Limited Formes galeniques d'oxcarbazepine
WO2007029093A2 (fr) * 2005-09-05 2007-03-15 Ranbaxy Laboratories Limited Formes galeniques de l'oxcarbazepine
WO2007053904A1 (fr) * 2005-11-10 2007-05-18 Alphapharm Pty Ltd Processus de regulation de la dimension de particule
WO2008037044A1 (fr) * 2006-09-27 2008-04-03 Medley S.A. Indústria Farmacêutica Formulation orale contenant oxcarbazépine et son procédé de production

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006046105A1 (fr) * 2004-10-25 2006-05-04 Ranbaxy Laboratories Limited Formes de dosage de l'oxcarbazepine
WO2007007182A2 (fr) * 2005-07-08 2007-01-18 Aurobindo Pharma Limited Formes galeniques solides d'agent antiepileptique

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998035681A1 (fr) * 1997-02-14 1998-08-20 Novartis Ag Comprimes d'oxacarbazepine enrobes par pelliculage
WO2002094774A2 (fr) * 2001-05-18 2002-11-28 Ranbaxy Laboratories Limited Formes galeniques d'oxcarbazepine
WO2007029093A2 (fr) * 2005-09-05 2007-03-15 Ranbaxy Laboratories Limited Formes galeniques de l'oxcarbazepine
WO2007053904A1 (fr) * 2005-11-10 2007-05-18 Alphapharm Pty Ltd Processus de regulation de la dimension de particule
WO2008037044A1 (fr) * 2006-09-27 2008-04-03 Medley S.A. Indústria Farmacêutica Formulation orale contenant oxcarbazépine et son procédé de production

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO2007121523A1 *

Also Published As

Publication number Publication date
EP2010499A4 (fr) 2012-07-18
AU2007242062A1 (en) 2007-11-01
WO2007121523A1 (fr) 2007-11-01

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