Stabilized prolonged release pharmaceutical composition comprising atypical antipsychotic

Abstract

The present invention provides stabilized prolonged release pharmaceutical compositions comprising atypical antipsychotic drug like paliperidone or pharmaceutically acceptable salts thereof without incorporating surfactant and for water penetration enhancer. Such compositions are preferably in the form of a matrix wherein one or more release controlling agents are present in and/or on the matrix. Further, such compositions comprise one or more release controlling agent and exhibits desired in vitro release of drug with or without lag period. The invention also provides a process for the preparation of such compositions.

We claim: 
     
         1 . A stabilized prolonged release surfactant free solid oral pharmaceutical tablet composition comprising a matrix core and a coating layer, wherein the matrix core comprises a mixture of:
 (a) a paliperidone or pharmaceutically acceptable salt thereof;   (b) at least one release controlling agent;   (c) at least one diluent; and optionally,   (d) at least one excipient selected from a binder, an anti-oxidant, and a mixture thereof; and   a coating layer comprising a mixture of ionic release controlling agent and non-ionic release controlling agent coated on the said matrix core;   wherein the release controlling agents in and on the matrix core ranges from 1% to 55% by weight of the matrix core.   
     
     
         2 . A composition as claimed in  claim 1 , wherein the release controlling agent in and on the matrix core is selected from the group consisting of carbomer, polyethylene oxide, ethyl cellulose, xanthan gum, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, sodium carboxymethylcellulose, carboxymethylcellulose, calcium carboxymethylethylcellulose, locust bean gum, methacrylic acid copolymers, polyvinylpyrrolidone, mixture of polyvinyl acetate and polyvinyl pyrrolidone, sodium alginate, hypromellose phthalate, polyvinyl acetate phthalate, hypromellose acetate succinate, cellulose acetate, shellac, polyvinyl alcohol, polyvinyl acetate, and mixtures thereof. 
     
     
         3 . A composition as claimed in  claim 1 , wherein the release controlling agent in and on the matrix core is selected from the group consisting of carbomer, polyethylene oxide, hydroxypropylmethylcellulose, hypromellose phthalate, cellulose acetate, ethylcellulose, and mixtures thereof. 
     
     
         4 . A composition as claimed in  claim 1 , wherein the mixture of ionic release controlling agent and non-ionic release controlling agent is in the ratio from 1:0.5 to 1:1. 
     
     
         5 . A composition as claimed in  claim 1 , wherein the release controlling agent in and on the matrix core is selected from the group consisting of a mixture of carbomer and polyethylene oxide, a mixture of hypromellose phthalate and hydroxypropylmethyl cellulose, a mixture of hypromellose phthalate and ethyl cellulose, and a mixture of carbomer and hydroxypropylmethyl cellulose. 
     
     
         6 . A composition as claimed in  claim 1 , wherein the release controlling agent in and on the matrix core is from 4% to 40% by weight of the matrix. 
     
     
         7 . A composition as claimed in  claim 1 , wherein paliperidone or a pharmaceutically acceptable salt thereof is from 0.1 to 20% by weight of the composition. 
     
     
         8 . A composition as claimed in  claim 1 , wherein the antioxidant is selected from the group consisting of butylated hydroxytoluene, butylated hydroxyanisole, tocopherols, propyl gallate, ascorbates, ascorbic acid, sodium ascorbate, potassium or sodium salts of sulphurous acid, and mixtures thereof. 
     
     
         9 . A composition as claimed in  claim 1 , wherein the release controlling agent in the matrix core is a mixture of ionic release controlling agent and non-ionic release controlling agent. 
     
     
         10 . A composition as claimed in  claim 1 , that upon dissolution testing releases 10% or less of paliperidone in two hours. 
     
     
         11 . A composition as claimed in  claim 1 , that upon dissolution testing releases 10% or less of paliperidone in three hours. 
     
     
         12 . A composition as claimed in  claim 1 , that upon dissolution testing releases 10% or less of paliperidone in four hours. 
     
     
         13 . A composition as claimed in  claim 1 , that upon dissolution testing releases 10% or less of paliperidone in five hours. 
     
     
         14 . A composition as claimed in  claim 1 , that upon dissolution testing releases 10% or less of paliperidone in six hours.