Dispersions of rasagiline citrate

Abstract

The subject invention provides a solid dispersion of rasagiline citrate, a composition and a process for the manufacture thereof.

What is claimed is: 
     
         1 . A solid dispersion of at least one polymeric pharmaceutical excipient and rasagiline or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The solid dispersion of  claim 1 , wherein the at least one polymeric pharmaceutical excipient is a water soluble polymeric pharmaceutical excipient. 
     
     
         3 . The solid dispersion of  claim 1  or  2 , wherein the pharmaceutically acceptable salt of rasagiline is rasagiline citrate. 
     
     
         4 . The solid dispersion of  claim 3 , wherein the rasagiline citrate is mono-rasagiline citrate. 
     
     
         5 . The solid dispersion of any one of  claims 1 - 4 , wherein the at least one polymeric pharmaceutical excipient is polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, or hydroxypropyl methylcellulose phthalate. 
     
     
         6 . The solid dispersion of any one of  claims 1 - 4 , wherein the at least one polymeric pharmaceutical excipient is a co-polymer. 
     
     
         7 . The solid dispersion of  claim 6 , wherein the co-polymer is polyvinylpyrrolidone-vinyl acetate or methacrylic acid-ethyl acrylate. 
     
     
         8 . The solid dispersion of  claim 7 , wherein the co-polymer is methacrylic acid-ethyl acrylate. 
     
     
         9 . The solid dispersion of any one of  claims 1 - 8 , wherein T g  of the solid dispersion is at least 20° C. higher than that of rasagiline or a pharmaceutically acceptable salt thereof. 
     
     
         10 . A pharmaceutical composition comprising the solid dispersion of any one of  claims 1 - 9 . 
     
     
         11 . A process for making the solid dispersion of any one of  claims 1 - 9 , comprising:
 a) combining a mixture of rasagiline free base and the at least one polymeric pharmaceutical excipient in a solvent to form a solution;   b) adding citric acid to the solution; and   c) removing the solvent from the solution.   
     
     
         12 . The process of  claim 11 , wherein the solvent is methanol, ethanol, acetone, dichloromethane, dioxane and water, or a mixture of at least two thereof. 
     
     
         13 . The process of  claim 11  or  13 , wherein step c) is performed at a temperature of between about 55° C. and 80° C. by rotary evaporation. 
     
     
         14 . The process of  claim 11  or  12 , wherein in step b) the solvent is removed by lyophilization. 
     
     
         15 . A process for making the solid dispersion of any one of  claims 1 - 9 , comprising:
 a) dissolving a mixture of rasagiline or the pharmaceutically acceptable salt thereof, and the at least one polymeric pharmaceutical excipient in a solvent to form a solution; and   b) removing the solvent from the solution.   
     
     
         16 . The process of  claim 15 , wherein the pharmaceutically acceptable salt of rasagiline is rasagiline citrate. 
     
     
         17 . The process of  claim 16 , wherein the rasagiline citrate is mono-rasagiline citrate. 
     
     
         18 . The process of any one of  claims 15 - 17 , wherein the solvent is methanol, ethanol, acetone, dichloromethane, dioxane and water, or a mixture of at least two thereof. 
     
     
         19 . The process of any one of  claims 15 - 18 , wherein step b) is performed at a temperature of between about 55° C. and 80° C. by rotary evaporation. 
     
     
         20 . The process of any one of  claims 15 - 18 , wherein in step b) the solvent is removed by lyophilization. 
     
     
         21 . A process for making the solid dispersion of any one  claims 1 - 9 , comprising:
 a) combining a mixture of rasagiline free base, the at least one polymeric pharmaceutical excipient, and citric acid; and   b) grinding the mixture.   
     
     
         22 . The process of  claim 21 , wherein step b) is performed by dry milling the mixture. 
     
     
         23 . The process of  claim 21 , wherein step b) is performed by wet milling the mixture with a solvent. 
     
     
         24 . The process of  claim 23 , wherein the solvent is methanol or acetone. 
     
     
         25 . The process of  claim 21 , wherein step b) is performed at a temperature below −100° C. 
     
     
         26 . A process for making the solid dispersion of any one of  claims 1 - 9 , comprising:
 a) obtaining a solid mixture of rasagiline or the pharmaceutically acceptable salt thereof, and the at least one polymeric pharmaceutical excipient; and   b) grinding the mixture.   
     
     
         27 . The process of  claim 26 , wherein the pharmaceutically acceptable salt of rasagiline is rasagiline citrate. 
     
     
         28 . The process of  claim 27 , wherein the rasagiline citrate is mono-rasagiline citrate. 
     
     
         29 . The process of any one of  claims 26 - 28 , wherein step b) is performed by dry milling the mixture. 
     
     
         30 . The process of claim any one of  claims 26 - 28 , wherein step b) is performed by wet milling the mixture with a solvent. 
     
     
         31 . The process of  claim 30 , wherein the solvent is methanol or acetone. 
     
     
         32 . The process of claim any one of  claims 26 - 28 , wherein step b) is performed at a temperature below −100° C. 
     
     
         33 . A method of treating a human subject afflicted with Parkinson's disease comprising administering to the human subject an amount of the pharmaceutical composition of  claim 10 , effective to treat the human subject.