Extended release pharmaceutical formulations

Abstract

The present invention relates to coated extended release pharmaceutical formulations of valsartan comprising a core comprising valsartan and at least one coating layer over the core. The present invention further relates to extended release pharmaceutical formulations comprising (a) a core comprising valsartan and at least one hydrophilic swelling polymer and (b) at least one coating layer over the core wherein the coating layer in contact with the core is applied from an organic solvent based system.

1 - 30 . (canceled) 
     
     
         31 . A controlled release gastroretentive oral dosage form, comprising:
 a gastroretentive core comprising
 (a) a therapeutically effective amount of valsartan of about 160 mg; and 
 (b) hydroxypropyl methylcellulose in an amount of not less than about 200 mg; and 
   a dual coating system surrounding the gastroretentive core:   wherein the dual coating system comprises a seal coating layer contacting the gastroretentive core; and   wherein not more than about 40% valsartan is released from the controlled release gastroretentive dosage form in 1 hour and not less than 75% is released over 8 hours.   
     
     
         32 . The oral dosage form of  claim 31 , further comprising:
 (c) microcrystalline cellulose in an amount of about 160 mg.   
     
     
         33 . A controlled release gastroretentive oral dosage form, comprising:
 a gastroretentive core comprising
 (a) a therapeutically effective amount of valsartan from about 160 mg to about 320 mg; and 
 (b) one or more biocompatible swelling agents in a total amount of the one or more swelling agents of not less than about 375 mg; and 
   a dual coating system surrounding the gastroretentive core;   wherein the dual coating system comprises a seal coating layer contacting the gastroretentive core; and   wherein not more than about 40% valsartan is released from the controlled release gastroretentive dosage form in 1 hour and not less than 75% is released over 8 hours.   
     
     
         34 . The oral dosage form of  claim 33 , further comprising a pore forming agent in an amount from about 60 mg to about 120 mg. 
     
     
         35 . The oral dosage form of  claim 33 , further comprising one or more solubilizers in an amount from about 160 mg to about 320 mg. 
     
     
         36 . The oral dosage form of  claim 35 , wherein said one or more solubilizers is selected from the group consisting of hydrophilic surfactants, lipophilic surfactants, and mixtures thereof. 
     
     
         37 . The oral dosage form of  claim 35 , wherein said one or more solubilizers is selected from the group consisting of PEG-20-glyceryl stearate, PEG-40 hydrogenated castor oil, PEG-6 corn oil, lauryl macrogol-32 glyceride, stearoyl macrogol glyceride, polyglyceryl-10 monodioleate, propylene glycol oleate, propylene glycol dioctanoate, propylene glycol caprylate/caprate, glyceryl monooleate, glycerol monolinoleate, glycerol monostearate, PEG-20 sorbitan monolaurate, PEG-4 lauryl ether, sucrose distearate, sucrose monopalmitate, polyoxyethylene-polyoxypropylene block copolymer, polyethylene glycol 660 hydroxystearate, sodium lauryl sulphate, sodium dodecyl sulphate, propylene glycol alginate, sodium taurocholate, sodium glycocholate, sodium deoxycholate, betains, polyethylene glycol, d-alpha-tocopheryl polyethylene glycol 1000 succinate, and mixtures thereof 
     
     
         38 . The oral dosage form of  claim 33 , wherein said one or more biocompatible swelling agents (b) is a hydrophilic polymer. 
     
     
         39 . The oral dosage form of  claim 38 , wherein said hydrophilic polymer is selected from the group consisting of polyethylene oxide, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, sodium carboxy methylcellulose, calcium carboxymethyl cellulose, methyl cellulose, polyacrylic acid, maltodextrin, pre-gelatinized starch, polyvinyl alcohol, and mixtures thereof. 
     
     
         40 . The oral dosage form of  claim 33 , wherein said one or more biocompatible swelling agents (b) is polyethylene oxide. 
     
     
         41 . The oral dosage form of  claim 33 , further comprising one or more swelling enhancers in a total amount of the swelling enhancers from about 150 mg to about 300 mg. 
     
     
         42 . The oral dosage form of  claim 41 , wherein said one or more swelling enhancers is selected from the group consisting of low-substituted hydroxypropyl cellulose, microcrystalline cellulose, cross-linked sodium or calcium carboxymethyl cellulose, cellulose fiber, cross-linked polyvinyl pyrrolidone, cross-linked polyacrylic acid, cross-linked Amberlite resin, alginates, colloidal magnesium-aluminum silicate, pregelatinised starch, sodium carboxymethyl starch, and mixtures thereof. 
     
     
         43 . The oral dosage form of  claim 41 , wherein said one or more swelling enhancers is cross-linked polyvinyl pyrrolidone. 
     
     
         44 . The oral dosage form of  claim 33 , wherein said dosage form is retained in the upper gastrointestinal tract of a patient for a time period of about 1 hour to about 12 hours. 
     
     
         45 . The oral dosage form of  claim 33 , further comprising one or more gas-generating agents. 
     
     
         46 . The oral dosage form of  claim 45 , wherein said one or more gas-generating agents is sodium bicarbonate. 
     
     
         47 . The oral dosage form of  claim 33 , further comprising a pharmaceutically acceptable carrier. 
     
     
         48 . The oral dosage form of  claim 33 , wherein the seal coating layer comprises at least one coating agent and at least one pharmaceutically acceptable coating excipient. 
     
     
         49 . The oral dosage form of  claim 48 , wherein the coating agent is a polymeric or non-polymeric coating agent or a combination thereof. 
     
     
         50 . The oral dosage form of  claim 49 , wherein the polymeric coating agent is hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl ethylcellulose, ethyl cellulose, polyvinylacetate, copolymers of polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, or any combinations thereof. 
     
     
         51 . The oral dosage form of  claim 48 , wherein the pharmaceutically acceptable coating excipient is a plasticizer, an anti-tacking agent, an opacifier, or a colorant, or any combinations thereof. 
     
     
         52 . The oral dosage form of  claim 33 , wherein the seal coating layer comprises hydroxypropyl methylcellulose. 
     
     
         53 . The oral dosage form of  claim 31 , wherein the seal coating layer comprises at least one coating agent and at least one pharmaceutically acceptable coating excipient.