Method of making solid dispersions of highly crystalline therapeutic compounds

Abstract

A process for preparing solid dispersions of highly crystalline compounds. The highly crystalline or thermally labile therapeutic compounds are processed in an extruder in combination with a solubilizing agent and optionally a plasticizer. The resulting extrudate features the therapeutic compound in an amorphous state. Particularly useful as the solubilizing agents are surfactants such as poloxamers.

1 . A method for making a solid dispersion comprising the steps of:
 combining a poorly soluble and crystalline therapeutic compound with a carrier and a solubilizing agent to form a mixture;   processing said mixture in an extruder while heating said mixture; and   extruding said mixture to form an extrudate, wherein said therapeutic compound in said extrudate is amorphous.   
   
   
       2 . The method of  claim 1 , further comprising the step of compressing said extrudate to form a solid oral dosage form. 
   
   
       3 . The method of  claim 1 , wherein said solubilizing agent is a poloxamer. 
   
   
       4 . The method of  claim 3 , wherein said poloxamer is poloxamer 188. 
   
   
       5 . The method of  claim 1 , wherein said heating is from a temperature of 50° C. to 175° C. 
   
   
       6 . The method of  claim 5 , where said heating is from a temperature of 150° to 170° C. 
   
   
       7 . The method of  claim 1 , wherein said solubilizing agent is present in said mixture from about 10% to about 40% by weight of the mixture. 
   
   
       8 . The method of  claim 1 , wherein said mixture further comprises a plasticizer. 
   
   
       9 . The method of  claim 1 , wherein said plasticizer is sorbitol. 
   
   
       10 . The method of  claim 1 , wherein said therapeutic compound has a melting point equal or greater than 200° C. 
   
   
       11 . A method for making a solid dispersion comprising the steps of:
 combining a poorly soluble and thermally labile therapeutic compound with a carrier and a solubilizing agent to form a mixture;   processing said mixture in an extruder while heating said mixture; and   extruding said mixture to form an extrudate, wherein said therapeutic compound in said extrudate is amorphous.   
   
   
       12 . The method of  claim 11 , further comprising the step of compressing said extrudate to form a solid oral dosage form. 
   
   
       13 . The method of  claim 11 , wherein said solubilizing agent is a poloxamer. 
   
   
       14 . The method of  claim 13 , wherein said poloxamer is poloxamer 188. 
   
   
       15 . The method of  claim 11 , wherein said heating is from a temperature of 50° C. to 175° C. 
   
   
       16 . The method of  claim 15 , wherein said heating is from a temperature of 150° C. to 170° C. 
   
   
       17 . The method of  claim 11 , wherein said solubilizing agent is present in said mixture from about 10% to about 40% by weight of the mixture. 
   
   
       18 . The method of  claim 11 , wherein said mixture further comprises a plasticizer. 
   
   
       19 . The method of  claim 18 , wherein said plasticizer is sorbitol. 
   
   
       20 . A method for making a solid dispersion comprising the steps of:
 combining midostaurin with a carrier and a solubilizing agent to form a mixture;   processing said mixture in an extruder while heating said mixture; and   extruding said mixture to form an extrudate, wherein said midostaurin in said extrudate is in an amorphous state.