Amorphous onapristone compositions and methods of making the same

Abstract

Amorphous forms of onapristone and methods of making such amorphous forms are provided. Amorphous forms can be characterized by their X-ray powder diffraction patterns and other properties.

1 . A method of making a stable amorphous onapristone comprising:
 mixing onapristone and water to form an onapristone solution;   mixing at least one equivalent of an acid solution with the onapristone solution;   mixing at least one equivalent of a base to the onapristone solution mixed with the at least one equivalent of the acid solution to form the stable amorphous onapristone precipitate,   wherein the XPRD pattern of the stable amorphous onapristone precipitate does not produce any substantially sharp scatter peaks.   
     
     
         2 . The method of  claim 1 , wherein the acid solution comprises an acid selected from the group consisting of hydrochloric acid, nitric acid, and sulfuric acid. 
     
     
         3 . The method of  claim 1 , wherein the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, and ammonium hydroxide. 
     
     
         4 . The method of  claim 1 , wherein the pH of is reduced to 1 or below when mixing at least one equivalent of an acid solution with the onapristone solution and the pH is increased to 10 or above to form the stable amorphous onapristone precipitate. 
     
     
         5 . (canceled) 
     
     
         6 . A composition comprising onapristone (25%) in a PVP VA64 copolymer matrix. 
     
     
         7 . A method of spray drying amorphous onapristone comprising, spray drying the composition of  claim 6  from a solution comprising about 8% w/w solids in methanol wherein the onapristone is amorphous. 
     
     
         8 . A composition comprising onapristone and a polymer, wherein the polymer is polyvinylpyrrolidone 30, polyethylene glycol 8000, polyethylene glycol 3350, or pyrrolidone K29/32, or any combination thereof. 
     
     
         9 . The composition of  claim 8 , wherein the composition comprises about 0.255 g of onapristone and about 0.777 g of polyvinylpyrrolidone. 
     
     
         10 . A method of making amorphous onapristone comprising:
 heating the composition of  claim 8  until the polymer and forms a polymer melt and the onapristone dissolves in the polymer melt forming a mixture; and   allowing the mixture to cool to room temperature and form a glassy solid comprising amorphous onapristone.   
     
     
         11 . The method of  claim 10 , wherein when the composition comprises polyvinylpyrrolidone 30, the onapristone content of the glassy solid is about 24% w/w. 
     
     
         12 . (canceled) 
     
     
         13 . The composition of  claim 8 , wherein the composition comprises about 0.241 g of onapristone and about 0.700 g of polyethylene glycol 8000. 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 10 , wherein when the composition comprises polyethylene glycol 8000, the onapristone content of the glassy solid is about 25% w/w. 
     
     
         16 . (canceled) 
     
     
         17 . The composition of  claim 8 , wherein the composition comprises about 0.238 g of onapristone and about 0.762 g of polyethylene glycol 3350. 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 10 , wherein when the composition comprises polyethylene glycol 3350, the onapristone content of the glassy solid is about 23% w/w. 
     
     
         20 . (canceled) 
     
     
         21 . The composition of  claim 8 , wherein the composition comprises about 0.249 g of onapristone and about 0.784 g of pyrrolidone K29/32. 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 10 , wherein when the composition comprises polyvinyl pyrrolidone K29/32, the onapristone content of the glassy solid is about 24% w/w. 
     
     
         24 . The composition of  claim 8 , wherein the composition comprises onapristone, polyvinyl pyrrolidone K29/32, and polyethylene glycol 3350. 
     
     
         25 . The composition of  claim 24 , wherein the composition comprises about 0.258 g of onapristone, about 0.202 g of polyvinyl pyrrolidone K29/32, and about 0.503 g of polyethylene glycol 3350. 
     
     
         26 . The composition of  claim 24 , wherein the composition comprises about 0.242 g of onapristone, about 0.373 g of polyvinyl pyrrolidone K29/32, and about 0.384 g of polyethylene glycol 3350. 
     
     
         27 . The composition of  claim 24 , wherein the composition comprises about 0.241 g of onapristone, about 0.547 g of polyvinyl pyrrolidone K29/32, and about 0.197 g of polyethylene glycol 3350. 
     
     
         28 . (canceled)