Aprepitant L-proline solvates—compositions and cocrystals
Aprepitant L-proline solvate compositions and aprepitant L-proline solvate cocrystals are disclosed as well as pharmaceutical compositions containing them. The compositions and cocrystals of the invention are: 1:1:1 aprepitant L-proline methanol composition; a 1:1:1 aprepitant L-proline methanol cocrystal; a 1:1:1:1 aprepitant L-proline ethanol composition; a 1:1:1 aprepitant L-proline ethanol cocrystal; 1 1:1:1 aprepitant L-proline n-propanol composition; and a 1:1:1 aprepitant L-proline n-propanol cocrystal: The aprepitant L-proline solvate compositions or cocrystals may be used in the same way as aprepitant to treat or prevent disorders relating to emesis, a neuropsychiatric disease, an inflammatory disease, pain, cancer, a skin disease, itch a respiratory disease, or an addiction.
1. An aprepitant L-proline solvate composition selected from a 1:1:1 aprepitant L-proline methanol composition, a 1:1:1 aprepitant L-proline ethanol composition, and a 1:1:1 aprepitant L-proline n-propanol composition.
2. An aprepitant L-proline solvate composition selected from a 1:1:1 aprepitant L-proline methanol cocrystal, a 1:1:1 aprepitant L-proline ethanol cocrystal, and a 1:1:1 aprepitant L-proline n-propanol cocrystal.
3. A pharmaceutical composition comprising an aprepitant L-proline composition of claim 1 and a pharmaceutically acceptable carrier.
4. A method of treating disorders relating to emesis comprising the step of administering to a patient in need thereof a therapeutically effective amount of an aprepitant L-proline composition of claim 1 .
5. A method of treating disorders relating to emesis comprising the step of administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 3 .
6. A 1:1:1 aprepitant L-proline methanol cocrystal characterised by at least one of:
a powder x-ray diffraction pattern having at least three peaks selected from the peaks at 7.1, 9.1, 10.5, 16.4, 21.6 and 21.9°2θ±0.2°2θ; and
a powder x-ray diffraction pattern substantially similar to FIG. 1 ; and
a P2 1 2 1 2 1 space group at 100K.
7. A pharmaceutical composition comprising a 1:1:1 aprepitant L-proline methanol cocrystal of claim 6 and a pharmaceutically acceptable carrier.
8. A method of treating disorders relating to emesis comprising the step of administering to a patient in need thereof a therapeutically effective amount of a 1:1:1 aprepitant L-proline methanol cocrystal of claim 6 .
9. A 1:1:1 aprepitant L-proline ethanol cocrystal characterised by at least one of:
a powder x-ray diffraction pattern having at least three peaks selected from the peaks at 7.2, 9.1, 10.4, 16.2, 21.6 and 22.0°2θ±0.2°2θ;
a powder x-ray diffraction pattern substantially similar to FIG. 9 ; and
a P2 1 2 1 2 1 space group at 100K.
10. A pharmaceutical composition comprising a 1:1:1 aprepitant L-proline ethanol cocrystal of claim 9 and a pharmaceutically acceptable carrier.
11. A method of treating disorders relating to emesis comprising the step of administering to a patient in need thereof a therapeutically effective amount of a 1:1:1 aprepitant L-proline ethanol cocrystal of claim 9 .
12. A 1:1:1 aprepitant L-proline n-propanol cocrystal characterised by at least one of:
a powder x-ray diffraction pattern having at least three peaks selected from the peaks at 6.3, 7.1, 9.0, 10.4, 13.7 and 17.3°2θ±0.2°2θ;
a powder x-ray diffraction pattern substantially similar to FIG. 14 ; and
a P2 1 2 1 2 1 space group at 100K.
13. A pharmaceutical composition comprising a 1:1:1 aprepitant L-proline n-propanol cocrystal of claim 12 and a pharmaceutically acceptable carrier.
14. A method of treating disorders relating to emesis comprising the step of administering to a patient in need thereof a therapeutically effective amount of a 1:1:1 aprepitant L-proline n-propanol cocrystal of claim 12 .
15. A pharmaceutical composition comprising an aprepitant L-proline cocrystal of claim 2 and a pharmaceutically acceptable carrier.
16. A method of treating disorders relating to emesis comprising the step of administering to a patient in need thereof a therapeutically effective amount of an aprepitant L-proline cocrystal of claim 2 .
17. A method of treating disorders relating to emesis comprising the step of administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 15 .
18. A method of treating disorders relating to emesis comprising the step of administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 7 .
19. A method of treating disorders relating to emesis comprising the step of administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 10 .
20. A method of treating disorders relating to emesis comprising the step of administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 13 .