Crystalline forms of an NK-1 antagonist
The present invention is related to crystalline forms of 2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethyl-N-(6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridin-3-yl)propanamide which is an NK-1 antagonist useful in the treatment of induced vomiting and other disorders.
1. A micronized non-solvated crystalline free-base form of the compound 2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethyl-N-(6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridin-3-yl)propanamide which comprises less than 1% impurities and exhibits an XRPD pattern substantially as shown in FIG. 28 .
2. The crystalline form of claim 1 which is substantially isolated and micronized.
3. A micronized pharmaceutical composition comprising a non-solvated crystalline free-base form of the compound 2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethyl-N-(6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridine-3-yl)propanamide which comprises less than 1% impurities and exhibits an XRPD pattern substantially as shown in FIG. 28 , and one or more pharmaceutically acceptable excipients.
4. A crystalline form of a trifluoroethanol solvate of the compound 2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethyl-N-(6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridine-3-yl)propanamide which is Form II.
5. A crystalline form of a formate salt of the compound 2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethyl-N-(6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridine-3-yl)propanamide which is Form III.
6. The pharmaceutical composition of claim 3 , in the form of a tablet, pill, powder, lozenge, sachet, cachet, elixir, suspension, emulsion, solution, syrup, aerosol, ointment, soft or hard gelatin capsule, suppository, sterile injectable solution, or sterile packaged powder.
7. The pharmaceutical composition of claim 3 , in the form of a tablet or capsule.
8. The compound of claim 1 , wherein the compound is in the form of particles wherein at least 90% of the particles are greater than 0.01 microns and less than 500 microns.
9. The compound of claim 1 , wherein the compound is in the form of particles wherein at least 90% of the particles are greater than 0.1 microns and less than 100 microns.
10. The composition of claim 3 , wherein the compound is in the form of particles wherein at least 90% of the particles are greater than 0.01 microns and less than 500 microns.
11. The composition of claim 3 , wherein the compound is in the form of particles wherein at least 90% of the particles are greater than 0.1 microns and less than 100 microns.
12. The compound of claim 1 wherein said non-solvated crystalline free-base form of 2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethyl-N-(6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridine-3-yl)propanamide comprises less than 0.5% impurities.
13. The composition of claim 3 wherein said non-solvated crystalline free-base form of 2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethyl-N-(6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridine-3-yl)propanamide comprises less than 0.5% impurities.