Single Unit Oral Dose Pharmaceutical Composition Comprising Levodopa, Carbidopa And Entacapone Or Salts Thereof

Abstract

There is provided a single unit oral dose pharmaceutical composition comprising a) levodopa or salts thereof from about 50 mg to about 300 mg in extended release form, b) carbidopa or salts thereof from about 10 mg to about 100 mg in extended release and c) entacapone or salts thereof from about 100 mg to about 1000 mg in immediate release form, optionally with other pharmaceutically acceptable excipients. The invention also relates to process of preparation of such compositions.

1 . A single unit oral dose pharmaceutical composition comprising a) levodopa or salts thereof from about 50 mg to about 300 mg in extended release form, b) carbidopa or salts thereof from about 10 mg to about 100 mg in extended release and c) entacapone or salts thereof from about 100 mg to about 1000 mg in immediate release form, optionally with other pharmaceutically acceptable excipients. 
     
     
         2 . A method of treating Parkinson's disease in a mammal, comprising administering to a mammal in need thereof, a single unit oral dose pharmaceutical composition comprising a) levodopa or salts thereof from about 50 mg to about 300 mg in extended release form, b) carbidopa or salts thereof from about 10 mg to about 100 mg in extended release and c) entacapone or salts thereof from about 100 mg to about 1000 mg in immediate release form, optionally with other pharmaceutically acceptable excipients. 
     
     
         3 . A method of reducing the “wearing off” phenomena in Parkinson's patients, comprising administering to patient in need thereof, a single unit oral dose pharmaceutical composition comprising a) levodopa or salts thereof from about 50 mg to about 300 mg in extended release form, b) carbidopa or salts thereof from about 10 mg to about 100 mg in extended release and c) entacapone or salts thereof from about 100 mg to about 1000 mg in immediate release form, optionally with other pharmaceutically acceptable excipients. 
     
     
         4 . A process for preparing a single unit oral dose pharmaceutical composition comprising a) levodopa or salts thereof from about 50 mg to about 300 mg in extended release form, b) carbidopa or salts thereof from about 10 mg to about 100 mg in extended release and c) entacapone or salts thereof from about 100 mg to about 1000 mg in immediate release form, wherein said process comprises of: a) coating or mixing levodopa, carbidopa with pharmaceutically acceptable rate controlling polymers; b) entacapone with one or more pharmaceutically acceptable excipients; c) mixing the blend of step a) and b) and converting it into suitable dosage form. 
     
     
         5 ) The composition as claimed in 1, wherein the composition comprises one or more of tablet, bilayered tablet, trilayered tablet, capsule, powder, disc, caplet, granules, pellets, granules in capsule, minitablets, minitablets in capsule, pellets in capsule and sachet. 
     
     
         6 ) The composition as claimed in  1 , wherein the extended release is achieved by coating or mixing levodopa and carbidopa with one or more pharmaceutically acceptable rate controlling polymers. 
     
     
         7 ) The composition as claimed in  6 , wherein the pharmaceutically acceptable rate controlling polymers comprise one or more of polyvinyl acetate, cellulose acetate, cellulose acetate butyrate, cellulose acetate propionate, ethyl cellulose, a fatty acid, a fatty acid ester, an alkyl alcohol, a wax, shellac, rosin, zein (prolamine from corn), povidone, kollidon SR, a poly(meth)acrylate, microcrystalline cellulose or poly(ethylene oxide), polyuronic acid salts, cellulose ethers, xanthan gum, tragacanth gum, gum karaya, guar gum, acacia, gellan gum locust bean gum, alkali metal salts of alginic acid or pectic acid, sodium alginate, potassium alginate, ammonium alginate, hydroxypropyl cellulose, hydroxy ethyl cellulose, hydroxypropyl methyl cellulose, carboxyvinyl polymers, polymerized gelatin, shellac, methacrylic acid copolymer type C NF, cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose propionate phthalate, polyvinyl acetate phthalate (PVAP), cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate, dioxypropyl methylcellulose succinate, carboxymethyl ethyl cellulose (CMEC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), and acrylic acid polymers and copolymers like methyl acrylate, ethyl acrylate, methyl methacrylate and/or ethyl methacrylate with copolymers of acrylic and methacrylic acid esters (Eudragit NE, Eudragit RL, Eudragit RS). 
     
     
         8 ) The pharmaceutical composition of  claim 1 , wherein one tablet of the said composition exhibits no significant difference in rate and/or extent of absorption of entacapone as compared to 2-4 tablets of 200 mg of immediate release entacapone commercially marketed as Comtan® and no significant difference in rate and/or extent of absorption of levodopa and carbidopa as compared to one tablet of Sinemet® CR administered at the interval of 3-4 hours. 
     
     
         9 ) The method of treatment of  claim 2 , wherein one tablet of the said composition exhibits no significant difference in rate and/or extent of absorption of entacapone as compared to 2-4 tablets of 200 mg of immediate release entacapone commercially marketed as Comtan® and no significant difference in rate and/or extent of absorption of levodopa and carbidopa as compared to one tablet of Sinemet® CR administered at the interval of 3-4 hours. 
     
     
         10 ) The method of reducing the “wearing off” phenomena of  claim 3 , wherein one tablet of the said composition exhibits no significant difference in rate and/or extent of absorption of entacapone as compared to 2-4 tablets of 200 mg of immediate release entacapone commercially marketed as Comtan® and no significant difference in rate and/or extent of absorption of levodopa and carbidopa as compared to one tablet of Sinemet® CR administered at the interval of 3-4 hours.