Polymorphs of darunavir

Abstract

The present invention provides novel solvated forms of darunavir and processes for there preparation. The present invention also provides novel process for preparation of darunavir amorphous form and pharmaceutical composition comprising it. Thus, for example, darunavir 2-methyl-2-butanol solvate was dissolved in methylene dichloride, distilled under vacuum at 45° C. to obtain a residue, cyclohexane was added to the residue and stirred for 30 hours at 20 to 25° C., and the separated solid was filtered, washed with cyclohexane and dried under vacuum at 50° C. for 12 hours to yield darunavir amorphous form.

1 . A darunavir C 5 -C 8  alcohol solvate. 
     
     
         2 . A process for the preparation of darunavir C 5 -C 8  alcohol solvate as defined in  claim 1 , which comprises crystallizing darunavir C 5 -C 8  alcohol solvate from a solution of darunavir in C 5 -C 8  alcohol solvent. 
     
     
         3 . The solvate according to  claim 1 , wherein the ratio of darunavir to C 5 -C 8  alcohol solvent ranges between 1:0.3 and 1:1.3. 
     
     
         4 . The solvate according to  claim 3 , wherein the ratio of darunavir to C 5 -C 8  alcohol solvent is about 1:1. 
     
     
         5 . The process according to  claim 2 , wherein the C 5 -C 8  alcohol solvent is selected from 2-methyl-2-butanol or n-pentanol. 
     
     
         6 . A process for the preparation of darunavir amorphous form, which comprises:
 a. dissolving darunavir in a solvent;   b. removing the solvent from the solution obtained in step (a) to obtain a residue;   c. slurrying the residue obtained in step (b) with aliphatic solvent or aromatic solvent; and   d. isolating darunavir amorphous form.   
     
     
         7 . The process according to  claim 6 , wherein the darunavir used in step (a) is darunavir in any solvated or hydrated or anhydrous form. 
     
     
         8 . The process according to  claim 7 , wherein the darunavir used in step (a) is darunavir C 5 -C 8  alcohol solvate such as 2-methyl-2-butanol solvate or n-pentanol solvate. 
     
     
         9 . The process according to  claim 6 , wherein the solvent used in step (a) is a solvent or mixture of solvents selected from dichloromethane, ethylene dichloride, chloroform and ethyl acetate. 
     
     
         10 . The process according to  claim 9 , wherein the solvent is dichloromethane. 
     
     
         11 . The process according to  claim 6 , wherein the aliphatic solvent or aromatic solvent used in step (c) is a solvent or mixture of solvents selected from cyclohexane, hexane, n-heptane, toluene and xylene. 
     
     
         12 . The process according to  claim 11 , wherein the aliphatic solvent is cyclohexane. 
     
     
         13 . A pharmaceutical composition comprising a darunavir amorphous form and a pharmaceutically acceptable excipient. 
     
     
         14 . The pharmaceutical composition as claimed in  claim 13 , wherein the pharmaceutical composition is used in a solid dosage forms. 
     
     
         15 . The pharmaceutical composition as claimed in  claim 14 , wherein the solid dosage forms for oral administration is include capsules, tablets, pills, powders and granules.