Methods for crystallization of drugs

Abstract

Methods are disclosed including methods for crystallizing a material such as a drug. An example method may include combining a nucleation initiator, a surfactant solution, and an amorphous form of a drug to form a drug precursor dispersion/suspension. The method may also include incubating the drug precursor dispersion/suspension to allow the drug to convert from the amorphous form to a crystalline form.

What is claimed is: 
     
         1 . A method for crystallizing a drug, the method comprising:
 forming a solvent solution;   forming a surfactant solution by adding a first portion of the solvent solution to a surfactant;   forming a nucleation initiator solution by adding a second portion of the solvent solution to a quantity of drug microcrystals;   mixing the nucleation initiator solution with a quantity of amorphous drug particles to form a drug mixture; and   adding the surfactant solution to the drug mixture.   
     
     
         2 . The method of  claim 1 , wherein the solvent solution includes heptane. 
     
     
         3 . The method of  claim 1 , wherein the solvent solution includes ethyl acetate. 
     
     
         4 . The method of  claim 1 , wherein the solvent solution includes ethyl acetate and heptane. 
     
     
         5 . The method of  claim 4 , wherein the ratio of ethyl acetate to heptane is in the range of about 1:4 to 1:30. 
     
     
         6 . The method of  claim 4 , wherein the ratio of ethyl acetate to heptane is in the range of about 1:4 to 1:20. 
     
     
         7 . The method of  claim 4 , wherein the ratio of ethyl acetate to heptane is in the range of about 1:20. 
     
     
         8 . The method of  claim 1 , wherein the surfactant solution includes polyoxyethylene (20) sorbitan monooleate. 
     
     
         9 . The method of  claim 1 , wherein the surfactant solution includes polyoxyethylene (80) sorbitan monooleate. 
     
     
         10 . The method of  claim 1 , wherein the quantity of drug microcrystals include everolimus drug microcrystals. 
     
     
         11 . The method of  claim 1 , wherein the quantity of amorphous drug particles includes amorphous everolimus drug particles. 
     
     
         12 . The method of  claim 1 , wherein adding the surfactant solution to the drug mixture forms a drug precursor dispersion, and further comprising incubating the drug precursor dispersion to form drug microcrystals. 
     
     
         13 . The method of  claim 12 , further comprising sonicating the drug precursor dispersion. 
     
     
         14 . The method of  claim 12 , further comprising filtering the drug microcrystals. 
     
     
         15 . The method of  claim 12 , further comprising drying the drug microcrystals. 
     
     
         16 . A method for crystallizing a drug, the method comprising:
 combining (a) a nucleation initiator mixed with a solvent and (b) an amorphous form of a drug with a surfactant to form a drug precursor dispersion/suspension; and   incubating the drug precursor dispersion/suspension to allow the drug to convert from the amorphous form to a crystalline form.   
     
     
         17 . The method of  claim 16 , wherein the solvent includes ethyl acetate and heptane. 
     
     
         18 . The method of  claim 16 , wherein the nucleation initiator includes everolimus microcrystals. 
     
     
         19 . The method of  claim 16 , wherein the amorphous form of the drug includes amorphous everolimus. 
     
     
         20 . A method for crystallizing a drug, the method comprising:
 combining (a) a nucleation initiator mixed with a solvent and (b) an amorphous form of a drug to form a drug precursor dispersion/suspension;   adding a surfactant solution to the drug precursor dispersion/suspension; and   incubating the drug precursor dispersion/suspension to allow the drug to convert from the amorphous form to a crystalline form.