Amorphous onapristone compositions and methods of making the same
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 precipitate comprising:
mixing onapristone and water to form an onapristone slurry;
mixing at least one equivalent of an acid solution with the onapristone slurry to form a onapristone solution, wherein the pH of the onapristone solution mixed with the acid is about 1 or below;
mixing at least one equivalent of a base to the onapristone solution to form the stable amorphous onapristone precipitate, wherein the pH of the onapristone solution mixed with the base is about 10 or above;
isolating the stable amorphous onapristone precipitate by filtration; and
drying the stable amorphous onapristone precipitate, wherein the dried stable amorphous onapristone precipitate remains amorphous for at least 25 weeks.
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 amorphous onapristone precipitate remains amorphous for at least 16.5 months.
5. The method of claim 1 , wherein the amorphous onapristone precipitate does not contain crystalline onapristone.
6. The method of claim 1 , wherein the XPRD pattern of the amorphous onapristone precipitate does not contain any sharp peaks.
7. The method of claim 1 , further comprising storing the dried stable amorphous under ambient conditions for at least 25 weeks, wherein the onapristone precipitate remains amorphous for the at least 25 weeks.