Solvent free amorphous rapamycin

Abstract

An improved process for coating implantable medical devices utilizes a number of techniques for improving the stability of therapeutic agents contained within the coating. The stability of the therapeutic agents may be improved by creating substantially solvent-free, amorphous forms of the therapeutic agents.

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         12 . An amorphous therapeutic agent administerable orally, parentarally, intravascularly, intranasally, intrabronchially, transdermally, rectally or via a stent coated therewith, the amorphous therapeutic agent formed by the process comprising:
 dissolving an amount of crystalline therapeutic agent in a solvent to form a solution;   adding an agent to the solution to precipitate the therapeutic agent from the solution;   filtering the precipitate;   washing the precipitate to remove impurities; and   drying the precipitate.   
     
     
         13 . The method of  claim 12 , wherein the solvent is at least one solvent. 
     
     
         14 . The method of  claim 12 , wherein the crystalline therapeutic agent is crystalline sirolimus, and the solvent is 2-propanol. 
     
     
         15 . The method of  claim 14 , wherein the agent is water. 
     
     
         16 . The method of  claim 15 , further comprising heating and mixing the crystalline therapeutic agent and the solvent to facilitate dissolution of the crystalline therapeutic agent in the solvent to form the solution. 
     
     
         17 . The method of  claim 12 , wherein the concentration of the crystalline therapeutic agent determines a time period to achieve the precipitate from the solution. 
     
     
         18 . The method of  claim 12 , wherein a glass transition temperature of the amorphous therapeutic agent renders the amorphous therapeutic agent stable at room temperature and pressure. 
     
     
         19 . The method of  claim 12 , wherein the crystalline therapeutic agent is a variant of rapamycin. 
     
     
         20 . The method of  claim 19 , wherein the variant of rapamycin includes at least all analogs, derivatives and conjugates that bind to FKBP12, and other immunophilins.