Amorphous and crystalline forms of aprepitant and processes for the preparation thereof

1. A crystallization polymorphic mixture, comprising at least about 5 weight %, based on the total weight of the mixture, of polymorph Form I or Form II of aprepitant, with the remaining amount of the mixture being the other polymorph form of aprepitant, wherein the crystallization polymorphic mixture has a D 90 particle size of less than about 50 microns.

2. The polymorphic mixture of claim 1 , comprising about 5 weight % to about 75 weight % of polymorph Form I of aprepitant and about 95 weight % to about 25 weight % of polymorph Form II of aprepitant.

3. The polymorphic mixture of claim 1 , comprising about 20 weight % (±5%) of polymorph Form I of aprepitant and about 80 weight % (±5%) of polymorph Form II of aprepitant.

4. The polymorphic mixture of claim 1 , comprising about 65 weight % (±5%) of polymorph Form I of aprepitant and about 35 weight % (±5%) of polymorph Form II of aprepitant.

5. The polymorphic mixture of claim 1 , comprising about 69 weight % of polymorphic Form I of aprepitant and about 31 weight % of polymorphic Form II of aprepitant.

6. The polymorphic mixture of claim 1 , comprising about 63 weight % of polymorphic Form I of aprepitant and about 37 weight % of polymorphic Form II of aprepitant.

7. A pharmaceutical composition comprising a therapeutically effective amount of the crystallization polymorphic mixture according to claim 1 and one or more pharmaceutically acceptable carriers, excipients, diluents or adjuvants.

8. A process for the preparation of a crystallization polymorphic mixture of polymorphic Forms I and II of aprepitant of claim 1 , the process comprising:

(a) providing a solution of aprepitant in one or more solvents capable of dissolving the aprepitant;

(b) adding an anti-solvent to the solution; and

(c) isolating the polymorphic mixture.

9. The process of claim 8 , wherein the solvent is an alcohol or a mixture of an alcohol and water and the anti-solvent is selected from the group consisting of water, alkane solvent, ether solvent, aromatic hydrocarbon solvent and mixtures thereof.

10. The process of claim 8 , wherein the solvent is methanol and the anti-solvent is water.

11. A pharmaceutical composition comprising a therapeutically effective amount of the amorphous aprepitant and the crystallization polymorphic mixture of Form I and Form II of claim 1 .

12. A pharmaceutical composition comprising a therapeutically effective amount of the crystallization polymorphic mixture according to claim 2 and one or more pharmaceutically acceptable excipients.

13. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition is in the form of a capsule.