Crystalline pharmaceutical and methods of preparation and use thereof
Novel crystalline polymorphic forms, Forms A, B, C, D, and E of a compound of Formula I, which has been found to be a potent inhibitor of LFA-1, are disclosed. Methods of preparation and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed in this invention.
1. A crystalline form of the compound of Formula I:
or a pharmaceutically acceptable salt thereof, having an X-ray powder diffraction pattern comprising the following peaks, in terms of 2θ, of about 18.2°, 21.4° and 22.7°.
2. A composition comprising the crystalline form of claim 1 , and a pharmaceutically acceptable carrier.
3. The composition of claim 2 , wherein the composition is substantially free of other crystalline forms of the compound of Formula I.
4. A crystalline form of the compound of Formula I:
or a pharmaceutically acceptable salt thereof, having a differential scanning calorimetry thermogram comprising an endothermic peak at about 145° C.
5. A composition comprising the crystalline form of claim 4 , and a pharmaceutically acceptable carrier.
6. The composition of claim 5 , wherein the composition is substantially free of other crystalline forms of the compound of Formula I.
7. A crystalline form of the compound of Formula I:
or a pharmaceutically acceptable salt thereof, having a thermogravimetric analysis spectrum comprising a mass loss of about 2.5% between room temperature and 180° C.
8. The crystalline form of claim 7 , having a thermogravimetric analysis spectrum substantially as shown in FIG. 7 .
9. A composition comprising the crystalline form of claim 7 .
10. The composition of claim 9 , wherein the composition is substantially free of other crystalline forms of the compound of Formula I.
11. A crystalline form of the compound of Formula I:
or a pharmaceutically acceptable salt thereof, having a Raman chromatograph substantially as shown in FIG. 5 .
12. A composition comprising the crystalline form of claim 11 .
13. The composition of claim 12 , wherein the composition is substantially free of other crystalline forms of the compound of Formula I.
14. The crystalline form of claim 1 , wherein the X-ray powder diffraction pattern further comprises two or more of the following peaks, in terms of 2θ, of about 5.7°, 7.6°, 9.7°, 10.1°, 17.5°, 18.8°, 19.4°, 20.0°, 21.1°, 23.2° and 24.6°.
15. The crystalline form of claim 1 , wherein the X-ray powder diffraction pattern further comprises the following peaks, in terms of 2θ, of about 5.7°, 7.6°, 9.7°, 10.1°, 17.5°, 18.8°, 19.4°, 20.0°, 21.1°, 23.2° and 24.6°.
16. The crystalline form of claim 1 , wherein the X-ray powder diffraction pattern is substantially as shown in FIG. 6 .
17. The crystalline form of claim 4 , wherein the differential scanning calorimetry thermogram is substantially as shown in FIG. 8 .