EP2020993A2 - Composition pharmaceutique solide de gabapentine - Google Patents

Composition pharmaceutique solide de gabapentine

Info

Publication number
EP2020993A2
EP2020993A2 EP07785797A EP07785797A EP2020993A2 EP 2020993 A2 EP2020993 A2 EP 2020993A2 EP 07785797 A EP07785797 A EP 07785797A EP 07785797 A EP07785797 A EP 07785797A EP 2020993 A2 EP2020993 A2 EP 2020993A2
Authority
EP
European Patent Office
Prior art keywords
gabapentin
hydroxypropylcellulose
composition according
composition
tablet
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Withdrawn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
EP07785797A
Other languages
German (de)
English (en)
Inventor
Sergio Lloret Perez
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.)
Combino Pharm SL
Original Assignee
Combino Pharm SL
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 Combino Pharm SL filed Critical Combino Pharm SL
Publication of EP2020993A2 publication Critical patent/EP2020993A2/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Withdrawn legal-status Critical Current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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants

Definitions

  • the present invention relates to solid pharmaceutical compositions of gabapentin that have good stability and good bioavailability of the active principle, and that can be used for preparing pharmaceutical forms of gabapentin for oral administration.
  • Gabapentin is the INN of 1-aminomethyl-l- cyclohexaneacetic acid, corresponding to the following formula
  • Gabapentin is used for treating cerebral diseases, for example as an antiepileptic, as well as for the treatment of neuropathic pain.
  • Gabapentin is known to have problems of stability, which arise in the manufacturing process of gabapentin and during storage, including in alkaline conditions.
  • Aerosil 200 The excipients were selected after laborious experimental work, since their catalytic activity cannot be predicted in a logical manner.
  • patent application WO-A-01/97612 states that the conditions mentioned in the previous patent application are not technically necessary for obtaining stable compositions of gabapentin.
  • Said patent application describes stable compositions of gabapentin that contain a concentration of anions of mineral acid above 20 ppm, and excipients that should be avoided according to the description of EP-A- 0414263. Criteria for selecting suitable excipients to form part of the gabapentin compositions are not proposed in said patent application either.
  • Patent application EP-A-0446570 describes gabapentin tablets that contain maize starch, microcrystalline cellulose, and hydrogenated soya oil as lubricant. The same composition is also described in patent applications WO-A-01/97612 and WO-A-01/97782. None of these includes data on the stability of the active principle in said tablet.
  • Controlled-release formulations of gabapentin that comprise a combination of an amphiphilic starch and hydrogenated vegetable oil are described in patent application WO-A-2005/099674.
  • a capsule comprising gabapentin, microcrystalline cellulose, magnesium stearate, silica, and less than 0.05 wt .% of sodium lauryl sulphate as solubilizer is described in patent application WO-A-2005/072736.
  • Patent application WO-A-2006/008295 also describes capsules that comprise gabapentin and a mixture of excipients formed from a calcium salt of a weak acid, for example tribasic calcium phosphate, and a lubricant selected from hydrogenated castor oil and glycerol behenate.
  • a diluent selected from the group comprising monosaccharide sugars, and derivatives of polysaccharides.
  • Another way of minimizing the degradation of gabapentin is to use stabilizing compounds.
  • patent application WO-A-02/26263 describes formulations that include a stabilizing compound that is able to reduce the ionic strength.
  • Said compound is selected from the following classes of compounds: volatile alcohols, non-volatile alcohols, liquids or - A - solids miscible with water, liquids or solids immiscible with water, liquid or solid surfactants, antioxidants, ketones and aldehydes.
  • Patent application WO-A-2005/051384 describes calcium carbonate as stabilizer for solid formulations of gabapentin.
  • a humectant is included for stabilizing gabapentin formulations.
  • Said humectant is selected from ethylene glycol, propylene glycol, butyl glycol, sorbitol, glycerol, or their esters with aliphatic acids.
  • the object of the present invention is a solid pharmaceutical composition comprising gabapentin as active principle.
  • a tablet of gabapentin that comprises said composition also forms part of the object of the invention.
  • the use of the compositions for the preparation of solid forms of gabapentin for administration by the oral route also forms part of the invention.
  • the present inventors have discovered that the incorporation of a hydrophobic compound in the intragranular phase, and a humectant in the extragranular phase, leads to the preparation of solid compositions of gabapentin that have good stability and good bioavailability of the gabapentin.
  • the object of the invention is a solid pharmaceutical composition that comprises:
  • an intragranular phase comprising:
  • a pharmaceutically effective amount of gabapentin i) a pharmaceutically effective amount of gabapentin, ii) a hydrophobic compound selected from the group comprising hydrogenated vegetable oils, esters of glycerol and fatty acids with a Ci 6 to C 22 chain, alcohols with a Ci ⁇ to C 22 chain, cetyl esters, microcrystalline wax, and/or mixtures thereof, and iii) an agglutinating agent, and
  • an extragranular phase that comprises a humectant selected from the group comprising anionic surfactants, polyoxyethylenated esters of sorbitan and fatty acids with a C 12 to Ci ⁇ chain, polyoxyethylenated fatty acids with a Ci ⁇ to C22 chain, and/or mixtures thereof.
  • a humectant selected from the group comprising anionic surfactants, polyoxyethylenated esters of sorbitan and fatty acids with a C 12 to Ci ⁇ chain, polyoxyethylenated fatty acids with a Ci ⁇ to C22 chain, and/or mixtures thereof.
  • the pharmaceutical composition of the invention is a solid composition comprising an intragranular phase and an extragranular phase. It is a solid composition that is of a granular appearance, but includes non- granulated particles of the extragranular phase.
  • the intragranular phase can be prepared by wet granulation of a mixture that comprises the active principle, a hydrophobic compound, and an agglutinating agent, according to conventional methods that are familiar to a person skilled in the art, such as those described in the book by Remington: The Science and
  • the extragranular phase comprises a humectant.
  • composition of the invention is prepared by mixing the intragranular phase with the extragranular phase, and then homogenizing the mixture.
  • the active principle is gabapentin, and is selected from the group comprising its pharmaceutically acceptable salts, solvated, hydrated, or anhydrous.
  • anhydrous gabapentin, gabapentin monohydrate, the sodium salt of gabapentin, and the calcium salt of gabapentin we may mention, for example, anhydrous gabapentin, gabapentin monohydrate, the sodium salt of gabapentin, and the calcium salt of gabapentin.
  • Gabapentin containing less than 20 ppm of chloride ions is preferably used in the compositions of the invention.
  • the physicochemical characteristics of said products, and of the other pharmaceutical excipients that are used for preparing the composition of the invention, are described in reference works that are accessible to a person skilled in the art, such as the Handbook of Pharmaceutical Excipients, 4th Edition, London, Pharmaceutical Press, 2003 [ISBN 0 85369 472 9] . These reference works also usually give the trade names under which said products are marketed.
  • the hydrophobic compound that forms part of the intragranular phase is selected from the group comprising hydrogenated vegetable oils, esters of glycerol and fatty acids with a Ci ⁇ to C 22 chain, alcohols with a Ci ⁇ to C 22 chain, cetyl esters, microcrystalline wax, and/or mixtures thereof.
  • the hydrophobic compound is a hydrogenated vegetable oil selected from the group comprising hydrogenated castor oil, hydrogenated cottonseed oil, hydrogenated soya oil, hydrogenated palm oil, and/or mixtures thereof. More preferably the hydrophobic compound that forms part of the intragranular phase of the compositions of the invention is hydrogenated castor oil.
  • esters of glycerol and fatty acids with C1 6 to C22 chain that can be used in the compositions of the invention include glycerol palmitate, glycerol stearate, glycerol palmitostearate, glycerol behenate, and/or mixtures thereof.
  • Alcohols with Ci 6 to C 22 chain that are suitable for use as hydrophobic compound in the compositions of the invention include cetyl alcohol, cetostearyl alcohol, stearyl alcohol, behenic alcohol, and/or mixtures thereof .
  • Cetyl esters which are defined as a mixture of esters of saturated fatty alcohols with C 14 to C 18 chain and saturated fatty acids with Ci 4 to Cis chain are also suitable for use in the compositions of the invention.
  • the microcrystalline wax comprises a mixture of saturated linear and randomly branched alkanes obtained from petroleum.
  • the length of the chains is in the range from C 41 to C 5 -7.
  • the agglutinating agent is a compound that is able to impart cohesive properties to the pulverulent materials constituting the intragranular phase, so that the characteristics of flowability of the composition are improved.
  • the agglutinating agent that is used for preparing the intragranular phase can be selected from the group comprising: hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, polyvinylpyrrolidone, carboxymethylcellulose sodium, carboxymethylcellulose calcium, and/or mixtures thereof.
  • the agglutinating agent used is hydroxypropylcellulose .
  • the extragranular phase of the composition of the invention comprises a humectant .
  • a humectant is a compound or mixture of compounds that facilitates the wetting of the pharmaceutical composition when it comes into contact with water, so that it contributes to its dissolution, and to release of the active principle.
  • the humectant is selected from the group comprising anionic surfactants, polyoxyethylenated esters of sorbitan and fatty acids with C12 to Ci ⁇ chain, polyoxyethylenated fatty acids with C1 6 to C22 chain, and/or mixtures thereof.
  • the anionic surfactants are compounds that possess one or more functional groups that become ionized in aqueous solution giving rise to organic ions with a negative charge, and are responsible for the surface activity, which include good wetting properties.
  • the humectant is an anionic surfactant.
  • anionic surfactants the following may be mentioned: soaps, alkyl sulphates, sulphonated paraffins, ⁇ -olefin sulphonates, dialkyl sulphosuccinates, alkylbenzene sulphonates, alkyl phosphates and alkyl polyether sulphates.
  • the humectant used is sodium lauryl sulphate .
  • Sodium lauryl sulphate belongs to the alkyl sulphate group and is the sodium salt of the sulphuric monoester of lauric alcohol. It is an anionic surfactant with good humectant properties that finds application in pharmaceutical, cosmetic, and detergent formulations.
  • anionic surfactant with good humectant properties is sodium docusate, which is included in the dialkyl sulphosuccinate group, and is the sodium salt of bis (2-ethylhexyl) sulphosuccinate.
  • the polyoxyethylenated esters of sorbitan and fatty acids with C 12 to Ci ⁇ chain are ionic surfactants that are prepared from sorbitan, obtained by dehydration of sorbitol, by esterification with the corresponding fatty acid, and then reaction with ethylene oxide in the presence of a catalyst.
  • sorbitan monolaurate polyethoxylated with 20 mol of ethylene oxide sorbitan monooleate polyethoxylated with 20 mol of ethylene oxide
  • sorbitol trioleate polyethoxylated with 20 mol of ethylene oxide sorbitol trioleate polyethoxylated with 20 mol of ethylene oxide.
  • the polyoxyethylenated fatty acids with Ci 6 to C 22 chain are non-ionic surfactants obtained from the reaction of a fatty acid with Cie to C22 chain with ethylene oxide in the presence of a catalyst. Consideration may also be given to esters of fatty acids with Ci 6 to C22 chain and a polyethylene glycol of molecular weight between 40 and 8000. Within this group we may mention, for example: stearate of polyethylene glycol 400, stearate of polyethylene glycol 6000. The number that accompanies the name of the product corresponds to the average molecular weight of the polyethylene glycol chain that is incorporated in the ester.
  • the amount of gabapentin can vary between 75% and 95% based on the total weight of the composition, preferably between 80% and 90% based on the total weight of the composition; the amount of hydrophobic compound can vary between 3% and 15% based on the total weight of the composition, preferably between 6% and 12% based on the total weight of the composition; the amount of humectant can vary between 1% and 5% based on the total weight of the composition, preferably between 2% and 4% based on the total weight of the composition, and the amount of agglutinating agent can vary between 1% and 5% based on the total weight of the composition, preferably between
  • compositions of the invention can be used for the preparation of solid pharmaceutical forms of gabapentin for administration by the oral route.
  • oral pharmaceutical forms are tablets, which can be obtained by mixing and homogenizing the compositions of the invention with suitable excipients, followed by compression.
  • the invention also relates to a tablet of gabapentin that comprises an amount of the composition of the invention that is sufficient to provide an effective unit dose of gabapentin, and at least one excipient .
  • the tablets of the invention comprise between 70 wt.% and 90 wt . % of the composition of the invention, and between 10 wt . % and 30 wt . % of at least one excipient. More preferably the tablets comprise between 75 wt . % and 85 wt . % of the composition of the invention, and between 15 wt . % and 25 wt . % of at least one excipient.
  • gabapentin is a very effective active principle for the treatment of cerebral diseases such as epilepsy and neuropathic pain, and has extremely low toxicity.
  • it is usually administered to adults at daily doses between 900 mg and 2400 mg, divided into three doses.
  • the tablets of the invention contain a unit dose that is between 300 mg and 800 mg of gabapentin.
  • the excipient can be selected from the group comprising diluents, disintegrants, lubricants, antiadherents, sweeteners, flavour enhancers, flavouring agents, and/or mixtures thereof.
  • the excipient can be incorporated either in the granulation stage for preparing the intragranular phase, or in the stage of mixing of the latter with the extragranular phase together with the humectant, or alternatively in both stages.
  • the diluents are inert excipients that facilitate compression of pulverulent materials and endow the tablets with strength. They can be incorporated both in the intragranular phase and in the extragranular phase. The following are included among the diluents that can be used: microcrystalline cellulose, cellulose powder, silicated cellulose, lactose monohydrate, anhydrous lactose, mannitol, sorbitol, sucrose, fructose, dextrose, and/or mixtures thereof.
  • the diluent used in the tablets of the invention is microcrystalline cellulose.
  • the disintegrants are excipients that cause the tablet to break up rapidly when placed in an aqueous medium, plus rapid disaggregation of the granules, so that the active principle is released quickly.
  • said excipients are incorporated in the extragranular phase.
  • the disintegrants can be selected from the group comprising: hydroxypropylcellulose of low degree of substitution, carboxymethylcellulose sodium, carboxymethylcellulose calcium, crospovidone, croscarmellose sodium, and/or mixtures thereof.
  • the disintegrant used is hydroxypropylcellulose of low degree of substitution.
  • the lubricants and antiadherents are excipients that reduce interparticle tension, prevent adhesion of the particles, and improve the flowability of granulated or pulverulent compositions.
  • the lubricants can be selected from the group comprising talc, alkaline earth salts of stearic acid, especially magnesium and calcium stearates, stearic acid, glycerol palmitostearate, stearyl fumarate, and/or mixtures thereof.
  • One of the antiadherents used most commonly is colloidal silica.
  • magnesium stearate is used as lubricant.
  • the tablets of this invention can in addition contain sweeteners, flavouring agents and flavour enhancers, with the aim of obtaining adequate organoleptic characteristics (aroma and taste) that will be acceptable to the patient.
  • sweeteners we may mention saccharin sodium, aspartame, mannitol, xylitol, sucrose, sorbitol and ammonium glycyrricinate, and among the flavouring agents and flavour enhancers we may mention flavours from fruits and plants, for example orange, anise, mint, etc.
  • the amount of excipient present in the tablets of the invention will vary depending on the type of excipient used.
  • the amount of diluent can be between 1% and 10% based on the total weight of the tablet, preferably between 3% and 7% based on the total weight of the tablet;
  • the amount of disintegrant can be between 5% and 15% based on the total weight of the tablet, preferably between 7% and 12% based on the total weight of the tablet;
  • the amount of lubricant can be between 0.5% and 3% based on the total weight of the tablet, preferably between 1% and 2% based on the total weight of the tablet.
  • the tablet preferably comprises gabapentin, hydrogenated castor oil as hydrophobic compound, sodium lauryl sulphate as humectant, hydroxypropylcellulose as agglutinating agent, microcrystalline cellulose as diluent, hydroxypropylcellulose of low degree of substitution as disintegrant, and magnesium stearate as lubricant.
  • the tablets of the invention comprise between 65 wt . % and 75 wt . % of gabapentin, between 5 wt . % and 7 wt . % of hydrogenated castor oil, between 1 wt . % and 3 wt . % of sodium lauryl sulphate, between 2 wt.% and 4 wt . % of hydroxypropylcellulose, between 3 wt.% and 7 wt . % of microcrystalline cellulose, between 7 wt.% and 12 wt.% of hydroxypropylcellulose of low substitution, and between 1 wt.% and 2 wt.% of magnesium stearate.
  • the tablets of the invention comprise between 68 wt.% and 72 wt.% of gabapentin, between 5.5 wt.% and 6.5 wt . % of hydrogenated castor oil, between 1.5 wt.% and 2.5 wt.% of sodium lauryl sulphate, between 2.5 wt . % and 3.5 wt . % of hydroxypropylcellulose, between 4 wt . % and 6.5 wt . % of microcrystalline cellulose, between 8 wt . % and 11.2 wt. % of hydroxypropylcellulose of low substitution, and between 1.2 wt . % and 1.8 wt . % of magnesium stearate.
  • the tablets of the invention can be prepared by methods that are familiar to a person skilled in the art, and are fully described in Remington's book cited above.
  • One possible way of preparing the tablet is for example as follows. Mix and sieve the active principle and the hydrophobic compound, and granulate said mixture by wet granulation by applying a solution of an agglutinating agent and a solvent, which can be water or an organic solvent. Dry the granulated mixture in a fluidized bed, and sieve. Then add the humectant to the dry granules previously prepared and carry out compression in a conventional machine. The excipient can be incorporated in the granulation stage, and/or before compression of the granular composition.
  • an outer layer of protective coating again using conventional techniques, for example by sugar coating or spraying.
  • the tablet includes in addition an outer coating layer.
  • LUSTRE CLEAR which is formed from a mixture of carragenate and microcrystalline cellulose, and in addition pigments and opacifiers such as titanium dioxide.
  • compositions of the invention it is also possible to prepare capsules that comprise an amount of the composition that is sufficient to provide an effective unit dose of gabapentin.
  • the unit dose of gabapentin is between 100 mg and 400 mg, since larger amounts of active principle require the use of excessively large capsules .
  • the capsules of the invention can be prepared by methods that are familiar to a person skilled in the art, and are well described in Remington's book previously cited; for example using a capsule filling machine in which the composition of the invention is distributed into hard gelatin capsules.
  • compositions of the invention have good stability both in normal storage conditions (36 months at a temperature of 25 ⁇ 2°C and relative humidity of 60 ⁇ 5%), and in accelerated stability conditions (12 months at a temperature of 30 ⁇ 2°C and relative humidity of 60 ⁇ 5%) .
  • the tablets prepared using the compositions of the invention have good stability in both storage conditions, and in all cases the lactam content remained below 0.4 wt . % determined by high-performance liquid chromatography (HPLC) .
  • HPLC high-performance liquid chromatography
  • the aforementioned mixture was mixed with the aqueous solution of hydroxypropylcellulose in a fast, high- shear granulator.
  • the mixture was dried in a fluidized bed at a temperature not above 40 0 C, and the dry granules were sieved at a mesh of 1 mm, thus obtaining the intragranular phase of the composition of the invention.
  • the mixture obtained was compressed in a rotary tablet press, obtaining 1000 tablets of gabapentin with a content of active principle of 800 mg.
  • the tablets were coated with an aqueous dispersion formed from 6.00 g of titanium dioxide, 26.00 g of LUSTRE CLEAR, and 320 g of water, so that the increase in tablet weight on applying the coating was about 3%.
  • the tablets obtained displayed good stability both in normal storage conditions (36 months at a temperature of 25 ⁇ 2°C and relative humidity of 60 ⁇ 5%), and in accelerated stability conditions (12 months at a temperature of 30 ⁇ 2°C and relative humidity of 60 ⁇ 5%) .
  • the water content was determined using the Karl Fischer method, which is familiar to a person skilled in the art.
  • the assay value, or content of active principle, and the content of lactam impurity were determined using HPLC following the method described in section 2.2.29 of the European Pharmacopoeia.
  • Tablet hardness was determined in the manner described in section 2.9.8 of the European Pharmacopoeia. Tablet disintegration in water was determined following the guidelines given in section 2.9.1 of the European Pharmacopoeia .
  • Microbiological quality was determined by the usual methods of microbiological control, such as those described in section 5.1.4 (Category 3) of the European Pharmacopoeia .
  • the dissolution profile exhibited by the tablets of the invention is suitable for releasing 100% of the active principle in a space of time of approximately 1 hour.
  • the dissolution test was performed according to the method described in section 2.9.3 of the European Pharmacopoeia .
  • the experimental conditions of said test are:
  • samples were taken at different times (5, 10, 15, 20, 30, 45 and 60 minutes), they were filtered through a 0.45 ⁇ m filter, and the gabapentin content was determined by HPLC.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Neurosurgery (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne des compositions pharmaceutiques solides de gabapentine présentant une bonne stabilité et une bonne biodisponibilité du principe actif, et pouvant être employées dans la préparation de formes pharmaceutiques solides de gabapentine pour l'administration par voie orale. La composition pharmaceutique selon l'invention est une composition solide contenant une phase intragranulaire et une phase extragranulaire. Il s'agit d'une composition solide d'apparence granulaire, contenant toutefois des particules non granulées de la phase extragranulaire. L'invention est caractérisée par l'intégration d'un composé hydrophobe dans la phase intragranulaire et d'un humectant dans la phase extragranulaire, permettant la fabrication de compositions solides de gabapentine présentant une bonne stabilité et une bonne biodisponibilité de la gabapentine.
EP07785797A 2006-05-08 2007-05-03 Composition pharmaceutique solide de gabapentine Withdrawn EP2020993A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES200601164A ES2288117B1 (es) 2006-05-08 2006-05-08 Composicion farmaceutica solida de gabapentina.
PCT/EP2007/003914 WO2007128495A2 (fr) 2006-05-08 2007-05-03 Composition pharmaceutique solide de gabapentine

Publications (1)

Publication Number Publication Date
EP2020993A2 true EP2020993A2 (fr) 2009-02-11

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EP07785797A Withdrawn EP2020993A2 (fr) 2006-05-08 2007-05-03 Composition pharmaceutique solide de gabapentine

Country Status (4)

Country Link
EP (1) EP2020993A2 (fr)
AR (1) AR060869A1 (fr)
ES (1) ES2288117B1 (fr)
WO (1) WO2007128495A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10010638B2 (en) 2016-06-14 2018-07-03 S. C. Johnson & Son, Inc. Wax melt with filler
US10342886B2 (en) 2016-01-26 2019-07-09 S.C. Johnson & Son, Inc. Extruded wax melt and method of producing same

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102009012788A1 (de) * 2009-03-13 2010-09-30 J. Rettenmaier & Söhne Gmbh + Co. Kg Verpressbares Tablettenmaterial mit ölhaltigem Wirkstoff, Tablette sowie Verfahren und Vorrichtung zu deren Herstellung
NZ773901A (en) 2015-04-01 2024-07-26 Akebia Therapeutics Inc Compositions and methods for treating anemia
WO2019036713A1 (fr) 2017-08-18 2019-02-21 Abbvie Inc. Formulations pharmaceutiques solides pour le traitement de l'endométriose, de fibromes utérins, du syndrome des ovaires polykystiques et de l'adénomyose
JP7374885B2 (ja) 2017-08-18 2023-11-07 アッヴィ・インコーポレイテッド 子宮内膜症、子宮筋腫、多嚢胞性卵巣症候群又は腺筋症を治療するための医薬製剤
GB2625579A (en) * 2022-12-21 2024-06-26 Novumgen Ltd An orally disintegrating tablet containing gabapentin or pharmaceutically acceptable salts thereof and the process of preparing the same

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT1183014E (pt) * 1999-06-14 2003-12-31 Cosmo Spa Composicoes farmaceuticas orais de libertacao controlada e de dissimulacao de sabor
US7056951B2 (en) * 2000-09-26 2006-06-06 Mutual Pharmaceutical Co., Inc. Stable solid dosage forms of amino acids and processes for producing same
ITMI20011337A1 (it) * 2001-06-26 2002-12-26 Farmatron Ltd Composizioni farmaceutiche orali a rilascio modificato del principio attivo
BR0215262A (pt) * 2001-12-20 2004-12-28 Pharmacia Corp Formas de dosagem com liberação sustentada de ordem zero e processo para a fabricação das mesmas
CN1668284A (zh) * 2002-06-07 2005-09-14 兰贝克赛实验室有限公司 加巴喷丁的缓释口服剂型
AU2003267732A1 (en) * 2002-10-08 2004-05-04 Ranbaxy Laboratories Limited Gabapentin tablets and methods for their preparation
GB0408308D0 (en) * 2004-04-14 2004-05-19 Vectura Ltd Pharmaceutical compositions

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2007128495A3 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10342886B2 (en) 2016-01-26 2019-07-09 S.C. Johnson & Son, Inc. Extruded wax melt and method of producing same
US10010638B2 (en) 2016-06-14 2018-07-03 S. C. Johnson & Son, Inc. Wax melt with filler

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WO2007128495A2 (fr) 2007-11-15
ES2288117B1 (es) 2008-12-01
ES2288117A1 (es) 2007-12-16
AR060869A1 (es) 2008-07-16
WO2007128495A3 (fr) 2008-05-02

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