Methods of preparing extrudates

Abstract

Compositions and methods of preparing amorphous drug formulations through hot melt extrusion which result in decreased decomposition of the desired drug are provided herein. Also provided are methods and compositions which further comprise a pharmaceutically acceptable thermoplastic polymer. In some embodiments, these compositions comprise a therapeutically active agent which is only sparingly soluble in water.

1 . An extrusion stock material composition comprising:
 (a) a mixture of a therapeutically active agent and a pharmaceutically acceptable thermoplastic polymer comprising from about 0.5% to about 55% w/w of a therapeutically active agent; and   (b) an organic solvent;   
       wherein the composition has a glass transition temperature (T g ) from about 40° C. to about 100° C. 
     
     
         2 . The composition of  claim 1 , wherein the glass transition temperature is from about 70° C. to about 90° C. 
     
     
         3 . (canceled) 
     
     
         4 . The composition of  claim 1 , wherein the amount of organic solvent is from about 0.5% w/w to about 45% w/w. 
     
     
         5 .- 6 . (canceled) 
     
     
         7 . The composition of  claim 1 , wherein the therapeutically active agent and the pharmaceutically acceptable thermoplastic polymer are soluble in the organic solvent. 
     
     
         8 . The composition of  claim 7 , wherein the therapeutically active agent and the pharmaceutically acceptable thermoplastic polymer have similar solubility in the organic solvent. 
     
     
         9 . The composition of  claim 1 , wherein the organic solvent is a volatile organic solvent. 
     
     
         10 .- 11 . (canceled) 
     
     
         12 . The composition of  claim 9 , wherein the organic solvent is a polar hydrocarbon, a polar aprotic solvent, or a polar protic solvent. 
     
     
         13 .- 21 . (canceled) 
     
     
         22 . The composition of  claim 1 , wherein the organic solvent comprises a mixture of two or more different organic solvents. 
     
     
         23 . The composition of  claim 22 , wherein the organic solvent is a mixture of solvents comprising at least one solvent selected from the group consisting of methanol, ethanol, isopropanol, acetone, tetrahydrofuran, or dichloromethane. 
     
     
         24 .- 27 . (canceled) 
     
     
         28 . The composition of  claim 1 , wherein the composition comprises a mixture of an amorphous therapeutically active agent and a pharmaceutically acceptable thermoplastic polymer. 
     
     
         29 . The composition of  claim 1 , wherein the composition comprises a therapeutically active agent which is rendered into the amorphous form following extrusion. 
     
     
         30 . The composition of  claim 1 , wherein the pharmaceutically acceptable thermoplastic polymer is a cellulosic polymer. 
     
     
         31 . (canceled) 
     
     
         32 . The composition of  claim 30 , wherein the pharmaceutically acceptable thermoplastic polymer is hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, cellulose acetate phthalate, or hydroxypropyl methyl cellulose acetate succinate. 
     
     
         33 .- 36 . (canceled) 
     
     
         37 . The composition of  claim 1 , wherein the pharmaceutically acceptable thermoplastic polymer is a non-cellulosic polymer. 
     
     
         38 . (canceled) 
     
     
         39 . The composition of  claim 37 , wherein the pharmaceutically acceptable thermoplastic polymer is poly(vinyl alcohol), poly(carboxylate), poly(ethylene glycol), poly(propylene glycol), polyvinyl pyrrolidone, copovidone, poloxamer, polymethylacrylate, polyacrylate, or a polymethacrylate or polyacrylate functionalized with a carboxylic acid group. 
     
     
         40 .- 45 . (canceled) 
     
     
         46 . The composition of  claim 1 , wherein the therapeutically active agent is an active agent which has a solubility in water of less than 5 mg/mL. 
     
     
         47 . (canceled) 
     
     
         48 . The composition of  claim 1 , wherein the therapeutically active agent is an agent which is known to undergo thermal degradation. 
     
     
         49 . (canceled) 
     
     
         50 . The composition of  claim 1 , wherein the composition further comprises one or more excipients. 
     
     
         51 . (canceled) 
     
     
         52 . A method of preparing an extrudate comprising:
 (a) obtaining an extrusion stock material composition of  claim 1 ; and   (b) transferring the extrusion stock material composition through an extruder to obtain an extrudate comprising the therapeutically active agent and the organic solvent.   
     
     
         53 .- 71 . (canceled) 
     
     
         72 . A method of preparing an extrudate comprising:
 (a) admixing an extrusion stock material composition of  claim 1  to a mixing apparatus;   (b) feeding the extrusion stock material composition through an extruder; and   (c) extruding the extrusion stock material composition from the press through a die to obtain an extrudate.   
     
     
         73 .- 115 . (canceled)