Composition of solifenacin or salt thereof for use in solid formulation

Abstract

A solid pharmaceutical preparation of solifenacin or a salt thereof, the preparation being stable and inhibited from decomposing with time when supplied to clinical fields. In a pharmaceutical preparation containing solifenacin or a salt thereof, the compound in an amorphous form was revealed to be causative of cardinal-drug decomposition with time. The composition for a solid pharmaceutical preparation of solifenacin or a salt thereof contains solifenacin or its salt each in a crystalline from, and the content provided are: a process for producing the composition; and a medicinal composition for solid pharmaceutical preparations which contains solifenacin and an amorphization inhibitor.

1 . A composition of solifenacin or a salt thereof for use in solid formulation, the composition containing the crystal of solifenacin or a salt thereof, wherein the amorphous content is within a range showing no influence on product stability. 
     
     
         2 . A composition of solifenacin or a salt thereof for use in solid formulation according to  claim 1 , wherein the amorphous content is 77 or less. 
     
     
         3 . A composition for use in solid formulation according to  claim 1  or  2 , which is produced by a manufacturing process including a step of blending solifenacin or a salt thereof with an excipient without using any solvent, followed by compressing-molding. 
     
     
         4 . A composition for use in solid formulation according to  claim 1  or  2 , which is produced by a manufacturing process including a step of adding a solvent to solifenacin or a salt thereof, wherein the amount of solifenacin or a salt thereof to be dissolved per 1 mL of the solvent is less than 0.1 mg. 
     
     
         5 . A composition for use in solid formulation according to  claim 4 , wherein the solvent added to solifenacin or a salt thereof is acetone or hexane or a mixture thereof. 
     
     
         6 . A composition for use in solid formulation according to  claim 1  or  2 , which is produced by a manufacturing process including a step of adding a solvent to prepare solifenacin or a salt thereof into an amorphous state, wherein the amount of solifenacin or a salt thereof to be dissolved per 1 mL of the solvent is 10 mg or more. 
     
     
         7 . A composition for use in solid formulation according to  claim 6 , wherein the solvent to prepare solifenacin or a salt thereof into an amorphous state is water, methanol or ethanol or a mixture thereof. 
     
     
         8 . A composition for use in solid formulation according to  claims 1  through  7 , which is manufactured by a manufacturing process including a step of promoting the crystallization of amorphous solifenacin or an amorphous salt thereof. 
     
     
         9 . A mixture of solifenacin or a salt thereof, wherein the mixture contains amorphous and crystalline solifenacin or an amorphous and crystal salt thereof and wherein the amorphous content of solifenacin or a salt thereof is within a range showing no influence on product stability. 
     
     
         10 . A pharmaceutical composition for use in solid formulation, the composition containing crystalline and amorphous solifenacin or a crystalline and amorphous salt thereof, together with an inhibitor of amorphous preparation. 
     
     
         11 . A pharmaceutical composition according to  claim 10 , wherein the inhibitor of amorphous preparation is a substance having ethylene oxide chain. 
     
     
         12 . A pharmaceutical composition according to  claim 11 , wherein the substance with ethylene oxide chain is polyethylene glycol.