Crystalline forms of 3-substituted 1,2,4-oxadiazole
The invention relates to crystalline forms of a 3-substituted 1,2,4-oxadiazole compound, methods of their preparation, and related pharmaceutical preparations thereof. The invention also relates to preparations suitable for pharmaceutical, veterinary, and agriculturally-relevant uses.
1. A crystalline compound having the structure of formula (I),
2. The crystalline compound of claim 1 , wherein the compound is solvated.
3. The crystalline compound of claim 1 , wherein the compound is a hydrate.
4. The crystalline compound of claim 3 , wherein the compound is a monohydrate.
5. The crystalline compound of claim 4 , having 2θ values 8.4±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 21.4±0.2, and 28.4±0.2.
6. The crystalline compound of claim 5 , having 2θ values 8.4±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 19.3±0.2, 20.4±0.2, 21.4±0.2, and 28.4±0.2.
7. The crystalline compound of claim 6 , having 2θ values 8.4±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 19.3±0.2, 19.9±0.2, 20.4±0.2, 21.4±0.2, 24.5±0.2, 26.5±0.2, and 28.4±0.2.
8. The crystalline compound of claim 7 , having 2θ values 8.4±0.2, 11.5±0.2, 13.6±0.2, 16.5±0.2, 16.8±0.2, 19.3±0.2, 19.9±0.2, 20.4±0.2, 21.4±0.2, 21.8±0.2, 24.5±0.2, 26.5±0.2, 27.5±0.2, 28.0±0.2, 28.4±0.2, 30.0±0.2, and 32.4±0.2.
9. The crystalline compound of claim 8 , having an XRD pattern substantially as shown in FIG. 1 .
10. The crystalline compound of claim 3 , wherein the compound is a dihydrate.
11. The crystalline compound of claim 10 , having 2θ values 12.9±0.2, 13.5±0.2, 15.7±0.2, 17.0±0.2, 29.7±0.2, and 33.7±0.2.
12. The crystalline compound of claim 11 , having 2θ values 12.9±0.2, 13.5±0.2, 15.7±0.2, 17.0±0.2, 20.3±0.2, 28.9±0.2, 29.7±0.2, and 33.7±0.2.
13. The crystalline compound of claim 12 , having 2θ values 12.9±0.2, 13.5±0.2, 15.7±0.2, 17.0±0.2, 19.6±0.2, 20.3±0.2, 26.2±0.2, 28.9±0.2, 29.7±0.2, and 33.7±0.2.
14. The crystalline compound of claim 13 , having 2θ values 12.9±0.2, 13.5±0.2, 15.7±0.2, 17.0±0.2, 19.1±0.2, 19.6±0.2, 20.3±0.2, 21.1±0.2, 21.4±0.2, 26.2±0.2, 27.2±0.2, 28.9±0.2, 29.7±0.2, 32.2±0.2, and 33.7±0.2.
15. The crystalline compound of claim 14 , having an XRD pattern substantially as shown in FIG. 2 .
16. A pharmaceutical composition comprising the crystalline compound of claim 1 and one or more pharmaceutically acceptable excipients.
17. A method for preparing the crystalline compound of claim 1 comprising the steps of:
a) providing a mixture comprising a compound of formula (I) and a solvent; and
b) crystallizing the compound of claim 1 from the mixture comprising the compound of formula (I).
18. The method of claim 17 , wherein the crystalline compound is a solvate.
19. The method of claim 18 , wherein the solvate is a hydrate.
20. The method of claim 17 , wherein the compound is monohydrate or a dihydrate.
21. The method of claim 17 , wherein the solvent is selected from acetonitrile, anisole, dichloromethane, ethanol, isopropyl acetate, methyl tert-butyl ether (MTBE), n-heptane, tetrahydrofuran, water, and mixtures thereof.
22. The method of claim 17 , wherein the mixture further comprises seed crystals.
23. The method of claim 22 , wherein the seed crystals are added at a weight percentage of the total mixture selected from about 1 wt %, about 2 wt %, about 3 wt %, about 4 wt %, about 5 wt %, about 6 wt %, about 7 wt %, about 8 wt %, about 9 wt %, and about 10 wt %.
24. The method of claim 22 , wherein the seed crystals are formula (I) Form 2 seed crystals.
25. The method of claim 17 , wherein the purity of the crystalline form of the compound of formula (I) is selected from about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, and about 99%.