Solid Composition Comprising Amorphous Sofosbuvir

Abstract

A solid composition comprising sofosbuvir and at least one pharmaceutically acceptable matrix compound wherein at least 99 weight-% of the sofosbuvir comprised in the composition are present in amorphous form, at least 99 weight-% of the solid composition consist of the sofosbuvir and the at least one matrix compound, and wherein the solid composition contains the sofosbuvir in an amount of at least 55 weight-% based on the combined weight of the sofosbuvir and the at least one matrix compound.

1 - 27 . (canceled) 
     
     
         28 : A process for the preparation of sofosbuvir of which at least 95 weight-% are present in its amorphous form, comprising
 (i) providing sofosbuvir in at least one crystalline form or in amorphous form or as a mixture of at least one crystalline form and amorphous form;   (ii) dissolving at least a portion of the sofosbuvir provided according to (i) in at least one solvent, obtaining a solution comprising the sofosbuvir;   (iii) subjecting at least a portion of the solution obtained according to (ii), to rapid-drying, obtaining the sofosbuvir of which at least 95 weight-% are present in its amorphous form;   or   (ii′) subjecting the sofosbuvir provided in (i) to a melt method, obtaining the sofosbuvir of which at least 95 weight-% are present in its amorphous form.   
     
     
         29 : The process of  claim 28 , wherein the at least one solvent according to (ii) is selected from the group consisting of water, C3-C6 ketones, C1-C2 halogenated hydrocarbons, C1-C4 alcohols, C2-C6 ethers, C3-C5 esters, and a combination of two or more thereof. 
     
     
         30 : The process of  claim 29 , wherein the at least one solvent according to (ii) is selected from the group consisting of water, C1-C4 alcohols, C3-C6 ketones, and a combination of two or more thereof. 
     
     
         31 : The process of  claim 30 , wherein the at least one solvent according to (ii) comprises water and a C1-C4 alcohol. 
     
     
         32 : The process of  claim 30 , wherein the at least one solvent according to (ii) comprises water and ethanol. 
     
     
         33 : The process of  claim 30 , wherein the at least one solvent according to (ii) comprises acetone. 
     
     
         34 : The process of  claim 28 , wherein the at least a portion of the solution obtained according to (ii) is subjected to rapid-drying after concentrating. 
     
     
         35 : The process of  claim 28 , wherein the rapid-drying is carried out by spray-drying or spray-granulation. 
     
     
         36 : The process of  claim 35 , wherein the rapid-drying is carried out by spray-drying. 
     
     
         37 : The process of  claim 36 , wherein the spray-drying is carried out at an inlet temperature in the range of from 50 to 100° C., and at an outlet temperature in the range of from 20 to 70° C. 
     
     
         38 : The process of  claim 28 , wherein the melt method is a hot-melt method. 
     
     
         39 : The process of  claim 28 , wherein the melt method is a hot-melt extrusion method. 
     
     
         40 : The process of  claim 28 , wherein at least 99 weight-% of the sofosbuvir are present in its amorphous form. 
     
     
         41 : The process of  claim 28 , wherein at least 99.9 weight-% of the sofosbuvir are present in its amorphous form.