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WO2007010508A2 - Compositions de metaxalone a liberation controlee - Google Patents

Compositions de metaxalone a liberation controlee Download PDF

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Publication number
WO2007010508A2
WO2007010508A2 PCT/IB2006/052538 IB2006052538W WO2007010508A2 WO 2007010508 A2 WO2007010508 A2 WO 2007010508A2 IB 2006052538 W IB2006052538 W IB 2006052538W WO 2007010508 A2 WO2007010508 A2 WO 2007010508A2
Authority
WO
WIPO (PCT)
Prior art keywords
metaxalone
composition according
composition
controlled release
dosage form
Prior art date
Application number
PCT/IB2006/052538
Other languages
English (en)
Other versions
WO2007010508A3 (fr
Inventor
Vivek Mishra
Rajan Kumar Verma
Hitesh Goel
Nitin Saigal
Narayanan Badri Viswanathan
Rajeev Singh Raghuvanshi
Ashok Rampal
Original Assignee
Ranbaxy Laboratories Limited
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 Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Publication of WO2007010508A2 publication Critical patent/WO2007010508A2/fr
Publication of WO2007010508A3 publication Critical patent/WO2007010508A3/fr

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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
    • A61K9/2022—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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug
    • 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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • 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
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
    • 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
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs

Definitions

  • the present invention relates to controlled release compositions of metaxalone for oral administration, and processes for their preparation.
  • Metaxalone 5-[(3,5-dimethyphenoxy) methyl] -2- oxazolidinone, is a skeletal muscle relaxant used to relieve the pain of muscle injuries, spasms, sprains, and strains. Metaxalone is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions. It is marketed under the brand name SKELAXIN ® , and is available in two strengths, 400 mg and 800 mg tablets. The general dosage for adults and children over 12 years of age is two 400 mg tablets (800 mg) or one 800 mg tablet, taken three to four times daily.
  • AHFS American Hospital Formulary Service
  • mean peak plasma concentrations are attained in 2 hours.
  • the onset of action is within 1 hour and duration of action is about 4 to 6 hours. It has a plasma half-life of 2-3 hours, thus requiring multiple dosing.
  • Repeated administration of a very high dosage drug effectuates patient inconvenience and is very bothersome for ambulatory patients, leading to poor patient compliance. Painful, musculoskeletal conditions require prompt relief; therefore, compositions exhibiting a quick onset of action are desirable.
  • poorly soluble, hydrophobic drug substances, such as metaxalone are administered in solid dosage forms, such as tablets or capsules, their rate of dissolution is rather slow.
  • U.S. Patent No. 4,722,938 describes methods of using musculoskeletal relaxants such as metaxalone.
  • WO 2004/019937 discloses a pharmaceutical composition that includes metaxalone and pharmaceutically acceptable excipients, characterized in that the pharmaceutical composition has enhanced oral bioavailability.
  • the metaxalone used may be a micronized, a salt form of metaxalone, a high-energy crystalline form of metaxalone or an amorphous metaxalone.
  • PCT International Publication No.
  • WO 2004/108067 discloses a programmed drug delivery system which is useful for targeted drug delivery to a specific site in the gastrointestinal tract, at which site the beneficial agent may be delivered as a pulse, or in a controlled manner.
  • U.S. patent application Ser. No. 20050063913 Al describes the composition comprising metaxalone particles having an effective average particle size of less than about 2000nm and at least one surface stabilizer that is preferably adsorbed to or associated with the surface of the drug particles.
  • metaxalone is indicated for acute painful musculoskeletal conditions that require quick relief it would be desirable to have a dosage form that maintains a balance between the amount of the drug released immediately and amount of drug released over an extended period. Further it is also desired to have a dosage form that maintains the plasma level of metaxalone without any troughs and peaks.
  • the time to achieve the Cmax in the plasma is often longer in the controlled release versus the immediate release formulation.
  • a long t max is particularly disadvantageous to patients seeking urgent treatment (especially in acute painful musculoskeletal conditions) and to maintain minimum effective concentration (MEC) levels.
  • MEC minimum effective concentration
  • a second difference in the pharmacokinetic profiles of controlled release in comparison to immediate release drug formulations is that the duration of sustained plasma levels is longer in the controlled release formulations.
  • the longer duration of such sustained plasma levels facilitated by controlled release formulations are advantageous to all patients, prolonging the desired biological effect. Therefore, although the controlled release formulation facilitates a substantially longer period of time in maintaining plasma levels of drug or active metabolite(s), it suffers from the drawback of requiring longer periods of time to achieve the C max , when compared to immediate release formulations.
  • a controlled release pharmaceutical composition for metaxalone that provides a therapeutically effective blood concentration level of metaxalone for a sustained period of time of up to at least twelve hours.
  • a controlled release pharmaceutical composition for metaxalone which includes a therapeutically effective amount of metaxalone and at least one rate controlling polymer, wherein the composition provides a constant release profile for a sustained period of time of up to at least twelve hours.
  • composition of the present invention may be a matrix-type dosage form, multiple unit dosage form or an osmotic dosage form.
  • the composition may be a matrix type dosage form, a reservoir type dosage form or combinations of both.
  • Matrix-type dosage forms are those in which the drug is distributed uniformly in the one or more rate controlling material and reservoir type dosage forms utilize polymeric coating over the core of the metaxalone.
  • a combination of the reservoir and matrix type includes extended or sustained release coatings on extended release matrices. - A -
  • Embodiments of the matrix type dosage form include one or more of the following features.
  • the matrix may be formulated into tablets of a single monolithic matrix, bilayered matrix or a multi-layered matrix.
  • the monolithic matrix may have a uniform mixture of the core containing metaxalone and one or more rate controlling polymers.
  • the monolithic matrix may have drug release profile tailored in a fashion to provide both immediate and controlled release profile.
  • the matrix may further include one or more pharmaceutically acceptable excipients.
  • the matrix-type dosage forms may be a bilayered type formulation comprising at least two layers which includes an extended release layer, and an immediate release layer.
  • the ratio of the immediate release metaxalone layer to the extended release metaxalone layer may range from about 20:80 to about 80:20 by weight.
  • the extended release layer may be a core and the immediate release layer may cover at least a portion of the core.
  • the extended release core may be a matrix and the matrix may have a uniform mixture of the metaxalone and one or more rate controlling polymers.
  • the controlled release metaxalone composition may be formulated as a multiple unit dosage form having plurality of discrete or aggregated particles, pellets, mini tablets, beads or granules. It another general aspect there is provided a controlled release metaxalone composition, in multiple unit dosage form, comprising at least two types of metaxalone - containing units which includes one immediate release unit, and another controlled release unit. The ratio of first unit to the second unit may range from about 20:80 to about 80:20 by weight.
  • the units containing metaxalone may include other pharmaceutically acceptable excipients.
  • the units can be filled into a capsule or compressed into a tablet dosage form.
  • the units may be coated with one or more layers comprising film forming agents and/or pharmaceutically acceptable excipients.
  • a controlled release metaxalone composition in an osmotic dosage form, which includes a core comprising metaxalone and a swelling agent, and a semi-permeable membrane coating surrounding the core and optionally, one or more additional layers of metaxalone below and/or above the semipermeable membrane for immediate release.
  • the ratio of immediate release metaxalone layer to the metaxalone core may range from about 20:80 to about 80:20 by weight.
  • the dosage form may further include one or more other pharmaceutically acceptable excipients.
  • metaxalone may be included in one or more forms.
  • the metaxalone may be micronized or nanonized. It may be used as a metaxalone adsorbate, or as an admixture of metaxalone-cyclodextrin.
  • the rate controlling polymers may include one or more of hydrophilic polymers, hydrophobic polymers, or combinations thereof.
  • the pharmaceutical composition may also include one or more pharmaceutically acceptable excipients.
  • the one or more pharmaceutically acceptable excipients may be fillers, binders, lubricants, glidants, colorants and flavoring agents.
  • a method of treating muscle spasm associated with acute, painful musculoskeletal conditions in a patient in need thereof includes administering a a controlled release pharmaceutical composition of metaxalone that provides a constant release profile for a sustained period of time of up to at least twelve hours.
  • Embodiments of the method may include one or more of the following features.
  • the dosage form may further include a non steroidal anti-inflammatory drug, analgesics or other pharmaceutical agents.
  • controlled release includes any type of controlled release such as prolonged release, sustained release, modified release and extended release.
  • matrix includes a uniform mixture of metaxalone, one or more rate controlling polymers and one or more pharmaceutically acceptable excipients.
  • the rate controlling polymers used in the matrix type dosage form may include one or more of hydrophilic polymers, hydrophobic polymers, or combinations thereof.
  • the hydrophilic rate-controlling polymers may include one or more of cellulose derivatives such as hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxy ethylcellulo se , hy droxymethylcellulo se , carboxymethylcellulo se , methylcellulose, sodium carboxy methylcellulose or combinations thereof; polyvinylpyrrolidone, polysaccharides, polyalkylene glycols, starch and derivatives; or mixtures thereof.
  • cellulose derivatives such as hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxy ethylcellulo se , hy droxymethylcellulo se , carboxymethylcellulo se , methylcellulose, sodium carboxy methylcellulose or combinations thereof
  • polyvinylpyrrolidone polysaccharides, polyalkylene glycols, starch and derivatives; or mixtures thereof.
  • the hydrophobic polymers may include one or more of ethyl cellulose, cellulose acetate, cellulose acetate butyrate, hydroxypropyl methylcellulose phthalate, poly (alkyl) methacrylate, and copolymers of acrylic or methacrylic acid esters, waxes, shellac and hydrogenated vegetable oils.
  • the osmotic controlled metaxalone dosage form may be prepared by blending metaxalone, at least one swelling agent, optionally an osmotic agent and one or more pharmaceutically acceptable inert excipient; and compressing the blend into a compact core; enclosing the core with a solution/dispersion of an enclosing composition comprising one or more semi-permeable membrane-forming polymers and other coating additives.
  • the immediate release metaxalone layer may be layered to cover at least a portion of the core, using a conventional coating pan, a spray coater, a rotating perforated pan, or an automated system, such as a centrifugal fluidizing (CF) granulator, a fluidized bed process, or any other suitably automated coating equipment.
  • CF centrifugal fluidizing
  • the swelling agents may include any pharmaceutically acceptable polymers, which swell in the presence of aqueous media.
  • cellulose derivatives for example, cellulose derivatives, starch, gums, alginates, acrylic acid derivatives, polyethylene oxides and carbohydrate based polymers.
  • the osmotic agents may be one or more of water soluble salts of inorganic acids, water soluble salts of organic acids, non ionic organic compounds having high water solubility, water-soluble amino acids, urea and urea derivatives.
  • the semi-permeable membrane of the osmotic dosage form is permeable to the passage of an external fluid, such as water and biological fluids, but is substantially impermeable to the passage of components in the internal compartment.
  • the materials useful for forming the wall are essentially nonerodible and are substantially insoluble in biological fluids during the life of the dosage form.
  • the semi-permeable membrane may be one or more of semi-permeable membrane-forming polymers and coating additives.
  • the semi-permeable membrane-forming polymers may be one or more of cellulose derivatives, starch, gums, alginates, acrylic acid derivatives and carbohydrate based polymers.
  • Flux-regulating agents can be admixed with the semi-permeable membrane to modulate the fluid permeability of the wall. For example, agents that produce a marked increase in permeability to fluid such as water are often essentially hydrophilic, while those that produce a marked permeability decrease to water are essentially hydrophobic.
  • Example of flux regulating agents include, but are not limited to, polyhydric alcohols, polyalkylene glycols and polyalkylenediols, polyesters of alkylene glycols.
  • the immediate release outer layer may further include film-forming polymers and optionally other pharmaceutically acceptable excipients.
  • the metaxalone used in the present invention may be in one or more forms such as metaxalone, micronized or nanonized metaxalone, metaxalone adsorbate and metaxalone-cyclodextrin admixture.
  • micronized or nanonized metaxalone Due to poor bioavailability of metaxalone, it can be used in a micronized or nanonized form.
  • the particle size of micronized or nanonized metaxalone may be in the range of 50nm to 50 ⁇ m.
  • the size reduction for micronization or nanonization may be carried out in any of the conventionally known methods using air jet mill, dyno mill, ball mill, colloid mill, grinding mill, roller mill, impact mill, etc.
  • the metaxalone adsorbate may be prepared by dissolving metaxalone and one or more of pharmaceutically acceptable surface modifiers in organic solvent and removing the solvent to co-precipitate the metaxalone adsorbate.
  • the pharmaceutically acceptable surface modifiers may be one or more of cellulose derivatives, starch, gums, sugars, saccharides, alcohols, alginates, surfactants, acrylic acid derivatives and carbohydrate based polymers.
  • cellulosic polymers include, but are not limited to, ethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, carboxymethylcellulose, cross-linked carboxymethylcellulose, hydroxymethylcellulose and hydroxyethylcellulose.
  • acrylic acid derivatives include, but are not limited to, polymethacrylates such as ethyl acrylate/methyl methacrylate copolymer (Eudragit NE- 30-D) and ammonio methacrylate copolymer types A and B (Eudragit RL30D and RS30D).
  • Suitable surfactants can be anionic, cationic, zwitterionic and nonionic surfactants.
  • compositions include at least one anionic surfactant.
  • anionic surfactants include but are not limited to alkyl sulfonates, alkyl phosphates, alkyl phosphonates, potassium laurate, sodium lauryl sulfate, sodium dodecylsulfate, alkyl polyoxyethylene sulfates, dioctyl sodium sulfo succinate, phosphatidyl glycerol, phosphatidylinositol, diphosphatidylglycerol, phosphatidyl inosine, phosphatidylserine, phosphatidic acid and their salts, cholic acid and other bile acids (e.g., cholic acid, deoxycholic acid, glycocholic acid, taurocholic acid, glycodeoxycholic acid) and salts thereof (e.g., sodium deoxycholate, etc.).
  • cholic acid and other bile acids e.g., cholic
  • Suitable examples of organic solvent may include one or more of ketones, such as acetone; alcohols, such as methanol, ethanol, isopropyl alcohol; and chlorinated hydrocarbons, such as methylene chloride.
  • Solvents may be removed by techniques known in the art, for example, one or more of distillation, distillation under vacuum, evaporation, and spray drying.
  • the metaxalone-cyclodextrin admixture may be prepared by blending metaxalone with cyclodextrin.
  • the admixture may also include one or more other pharmaceutically acceptable excipients.
  • the cyclodextrin may be a naturally occurring dextrin and also the methylated derivatives of these natural products, especially of beta-cyclodextrin.
  • the matrix may further include one or more pharmaceutically acceptable excipients.
  • the one or more pharmaceutically acceptable excipients may be fillers, binders, lubricants, glidants, colorants or flavoring agents.
  • fillers include, but are not limited to, corn starch, lactose, white sugar, sucrose, sugar compressible, sugar confectioners, glucose, sorbitol, calcium carbonate, calcium phosphate-dibasic, calcium phosphate-tribasic, calcium sulfate, microcrystalline cellulose, silicified microcrystalline cellulose, cellulose powdered, dextrates, dextrins, dextrose, fructose, kaolin, lactitol, mannitol, sorbitol, starch, starch pregelatinized, sucrose, and mixtures thereof.
  • binders include, but are not limited to, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, poloxamer, gelatin, gum Arabic, ethyl cellulose, polyvinyl alcohol, pullutan, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol, and mixtures thereof.
  • lubricants and glidants include, but are not limited to, colloidal anhydrous silica, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated castor oil, sucrose esters of fatty acids, microcrystalline wax, yellow beeswax, white beeswax, and mixtures thereof.
  • the coloring agents of the present invention may be selected from any FDA approved color for oral use.
  • composition may be formulated into various pharmaceutical preparations for oral administration, e.g., in the form of a tablet or capsule in accordance with any of the conventional procedures known in the field of art, for example, simple granulation followed by sieving; extrusion and marumerization or spheronization; rotogranulation; pelletization; micropelletization, compression, coating etc. These steps may be carried out in a conventional manner.
  • the bilayered or multilayered tablets prepared by the present invention may optionally be coated with one or more layers comprising film forming agents and/or pharmaceutically acceptable excipients.
  • the bilayered or multilayered tablets may be prepared by multiple-compression tablets comprising an inner core and an outer coat of metaxalone, and may be prepared such that one surface of the inner core is exposed.
  • These types of tablets are also referred to as inlay or bull's-eye tablets and these are similar to compression-coated tablets except that one surface of the coating is eliminated.
  • Suitable film forming polymers include one or more of ethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, cellulose acetate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, waxes, methacrylic acid polymers such as Eudragit® RL and RS, and mixtures thereof.
  • the coating can also be performed using any commercially available ready to coat preparations such as opadry-AMB, opadry-white, opadry-clear, etc.
  • Suitable solvents used for making a solution/suspension of film forming polymer include one or more of methylene chloride, isopropyl alcohol, acetone, methanol, ethanol, water and mixtures thereof.
  • the controlled release pharmaceutical composition for metaxalone of the present invention may be used for treating muscle spasm associated with painful musculoskeletal conditions in humans, by administering a controlled release pharmaceutical composition for metaxalone that provides a constant release profile for a sustained period of time up to at least twelve hours.
  • the method may further include administering in combination with other medicines, for example, other non-steroidal anti-inflammatory agents (NSAIDs), any analgesics or other pharmaceutically active agents, etc.
  • NSAIDs non-steroidal anti-inflammatory agents
  • any analgesics or other pharmaceutically active agents etc.
  • Example 1 illustrate various aspects of the present inventions. These examples are for illustration only and do not limit the scope of the inventions.
  • Example 1 illustrate various aspects of the present inventions. These examples are for illustration only and do not limit the scope of the inventions.
  • Metaxalone, poloxamer, lactose monohydrate, microcrystalline cellulose and hydroxypropyl methylcellulose were mixed well and granulated with polyvinyl pyrrolidone solution.
  • Metaxalone, poloxamer, lactose monohydrate, microcrystalline cellulose and sodium starch glycollate were mixed well and granulated with polyvinyl pyrrolidone solution.
  • the dried granules were mixed with magnesium stearate and colloidal anhydrous silica.
  • Metaxalone was dissolved in methylene chloride with constant stirring. Polyvinyl pyrrolidone and cross-linked carboxymethylcellulose were dispersed in it. Methylene chloride was removed to obtain metaxalone adsorbate for further formulation work.
  • Example 3
  • Metaxalone adsorbate of example 2 poloxamer, lactose monohydrate, microcrystalline cellulose and hydroxypropyl methylcellulose were mixed well and granulated with polyvinyl pyrrolidone solution.
  • the granules were dried and blended with magnesium stearate, colloidal anhydrous silica and talc.
  • Metaxalone adsorbate of example 2 poloxamer, lactose monohydrate, microcrystalline cellulose and sodium starch glycollate were mixed well and granulated with polyvinyl pyrrolidone solution.
  • the two types of granules were compressed into bilayered tablets using appropriate tooling.
  • Metaxalone and hydroxypropyl methylcellulose were mixed well and layered over the sugar spheres 2.
  • Ethylcellulose, hydroxypropyl methylcellulose and triacetin are mixed and coated over the metaxalone layered sugar spheres
  • the immediate release layer of metaxalone was provided by again layering metaxalone and hydroxypropyl methylcellulose over the coated spheres of step 2.
  • Example 5 The prepared spheres were blended in a desired weight ratio and filled in appropriate size capsule.
  • Example 5 The prepared spheres were blended in a desired weight ratio and filled in appropriate size capsule.
  • Metaxalone and Hydroxypropyl methylcellulose were mixed well and layered over the sugar spheres
  • Example 6 The two types of pellets were blended in a desired weight ratio and filled in to the capsules of suitable size.
  • Example 6 The two types of pellets were blended in a desired weight ratio and filled in to the capsules of suitable size.
  • Metaxalone, Lactose, sodium lauryl sulphate, and Hydroxypropyl methylcellulose were blended well and granulated with Polyvinylpyrrolidone solution.
  • the granules were dried and mixed with magnesium stearate and colloidal anhydrous silica.
  • Metaxalone, microcrystalline cellulose, sodium lauryl sulphate, and sodium starch glycollate were blended well and granulated with Polyvinylpyrrolidone solution. 2. The granules were dried and mixed with magnesium stearate and colloidal anhydrous silica.
  • the granules were dried and mixed with magnesium stearate and colloidal anhydrous silica.
  • Metaxalone adsorbate of example 2 Lactose, sodium lauryl sulphate, and Hydroxypropyl methylcellulose were mixed well and granulated with Polyvinylpyrrolidone solution.
  • the granules were dried and mixed with magnesium stearate and colloidal anhydrous silica.
  • the tablets prepared in the example 6 were subjected to in-vitro dissolution under the following conditions:
  • the tablets prepared in the example 7 - 10 were subjected to in-vitro dissolution under the following conditions:

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Abstract

La présente invention concerne des compositions de métaxalone à libération contrôlée, destinées à être administrées par voie orale, et des procédés pour les préparer.
PCT/IB2006/052538 2005-07-22 2006-07-24 Compositions de metaxalone a liberation controlee WO2007010508A2 (fr)

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IN1934/DEL/2005 2005-07-22
IN1934DE2005 2005-07-22

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WO2007010508A3 WO2007010508A3 (fr) 2007-09-13

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009019662A2 (fr) * 2007-08-09 2009-02-12 Ranbaxy Laboratories Limited Compositions à base de métaxolone orale

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1362585A2 (fr) * 2001-01-26 2003-11-19 Osmotica Corp. Compositions pharmaceutiques contenant un inhibiteur de cox-ii et un relaxant musculaire
WO2004066981A1 (fr) * 2003-01-29 2004-08-12 Sun Pharmaceutical Industries Limited Composition pharmaceutique orale a liberation controlee contenant du metaxalone en tant qu'agent actif
WO2005016310A1 (fr) * 2003-08-08 2005-02-24 Elan Pharma International Ltd. Nouvelles compositions de metaxalone
WO2005048996A2 (fr) * 2003-11-14 2005-06-02 Eurand, Inc. Formes posologiques a liberation modifiee de relaxants des muscles du squelette

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1362585A2 (fr) * 2001-01-26 2003-11-19 Osmotica Corp. Compositions pharmaceutiques contenant un inhibiteur de cox-ii et un relaxant musculaire
WO2004066981A1 (fr) * 2003-01-29 2004-08-12 Sun Pharmaceutical Industries Limited Composition pharmaceutique orale a liberation controlee contenant du metaxalone en tant qu'agent actif
WO2005016310A1 (fr) * 2003-08-08 2005-02-24 Elan Pharma International Ltd. Nouvelles compositions de metaxalone
WO2005048996A2 (fr) * 2003-11-14 2005-06-02 Eurand, Inc. Formes posologiques a liberation modifiee de relaxants des muscles du squelette

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009019662A2 (fr) * 2007-08-09 2009-02-12 Ranbaxy Laboratories Limited Compositions à base de métaxolone orale
WO2009019662A3 (fr) * 2007-08-09 2009-08-13 Ranbaxy Lab Ltd Compositions à base de métaxolone orale

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