Solid forms comprising (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, compositions thereof, and uses thereof
Solid forms comprising (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, compositions comprising the solid forms, methods of making the solid forms and methods of their use are disclosed. The methods include methods of treating and/or preventing disorders ameliorated by the reduction of levels of TNF-α or the inhibition of PDE4.
1. A method of treating psoriasis, which comprises orally administering to a patient having psoriasis about 20 mg twice daily of an unsolvated crystal form of the compound of Formula (I):
which is enantiomerically pure, wherein the crystal form is Form A or Form F; and wherein the patient achieves at least about a 50% reduction in Psoriasis Area and Severity Index score compared to baseline.
2. The method of claim 1 , wherein the psoriasis is moderate to severe plaque-type psoriasis.
3. The method of claim 1 , wherein the patient achieves at least about a 75% reduction in Psoriasis Area and Severity Index score compared to baseline.
4. The method of claim 1 , wherein the patient achieves at least about a 90% reduction in Psoriasis Area and Severity Index score compared to baseline.
5. The method of claim 1 , wherein the crystal form is administered in the form of a tablet or capsule.
6. The method of claim 1 , wherein the crystal form is Form A, which has an X-ray powder diffraction pattern comprising peaks at about 8.1, 14.4, 17.4, 23.6 and 25.1 degrees 2θ.
7. The method of claim 1 , wherein the crystal form is Form A, which has an X-ray powder diffraction pattern comprising peaks at about 8.1, 14.4, 15.2, 17.4, 18.4, 19.2, 20.5, 22.8, 23.2, 23.6, 24.5 and 25.1 degrees 2θ.
8. The method of claim 1 , wherein the crystal form is Form A, which has an X-ray powder diffraction pattern matching the pattern depicted in FIG. 1 .
9. The method of claim 1 , wherein the crystal form is Form A, which has a differential scanning calorimetry plot comprising an endothermic event with an onset temperature of about 155° C.
10. The method of claim 1 , wherein the crystal form is Form A, which has a differential scanning calorimetry plot matching the plot depicted in FIG. 2 .
11. The method of claim 1 , wherein the crystal form is Form A, which has a thermal gravimetric analysis plot comprising a mass loss of less than about 1% when heated from about 25° C. to about 140° C.
12. The method of claim 11 , wherein the mass loss is about 0.05%.
13. The method of claim 1 , wherein the crystal form is Form A, which has a thermal gravimetric analysis plot matching the plot depicted in FIG. 3 .
14. The method of claim 1 , wherein the crystal form is Form A, which exhibits a mass increase of less than about 1% when subjected to an increase in relative humidity from about 0% to about 95% relative humidity.
15. The method of claim 14 , wherein the mass increase is about 0.4%.
16. The method of claim 1 , wherein the crystal form is Form A, which has a moisture sorption isotherm plot matching the plot depicted in FIG. 4 .
17. The method of claim 1 , wherein the crystal form is Form A, which is stable upon exposure to about 40° C. and about 75% relative humidity for about 4 weeks.
18. The method of claim 1 , wherein the crystal form is Form F, which has an X-ray powder diffraction pattern comprising peaks at about 8.1, 15.6, 17.3 and 25.4 degrees 2θ.
19. The method of claim 1 , wherein the crystal form is Form F, which has an X-ray powder diffraction pattern comprising peaks at about 8.1, 8.6, 15.6, 17.3, 19.3, 21.4, 22.8, 24.6, 25.4, 25.9, 26.6 and 27.7 degrees 2θ.
20. The method of claim 1 , wherein the crystal form is Form F, which has an X-ray powder diffraction pattern matching the pattern depicted in FIG. 21 .
21. The method of claim 1 , wherein the crystal form is Form F, which has a differential scanning calorimetry plot comprising an endothermic event with an onset temperature of about 145° C.
22. The method of claim 1 , wherein the crystal form is Form F, which has a differential scanning calorimetry plot matching the plot depicted in FIG. 22 .
23. The method of claim 1 , wherein the crystal form is Form F, which has a thermal gravimetric analysis plot comprising a mass loss of less than about 1% when heated from about 25° C. to about 180° C.
24. The method of claim 23 , wherein the mass loss is about 0.1%.
25. The method of claim 1 , wherein the crystal form is Form F, which has a thermal gravimetric analysis plot matching the plot depicted in FIG. 23 .
26. The method of claim 1 , wherein the crystal form is Form F, which exhibits a mass increase of less than about 1% when subjected to an increase in relative humidity from about 0% to about 95% relative humidity.
27. The method of claim 26 , wherein the mass increase is about 0.2%.
28. The method of claim 1 , wherein the crystal form is Form F, which has a moisture sorption isotherm plot matching the plot depicted in FIG. 24 .
29. The method of claim 1 , wherein the crystal form is Form F, which is stable upon exposure to about 40° C. and about 75% relative humidity for about 4 weeks.
30. The method of claim 5 , wherein the crystal form is administered in the form of a capsule.
31. The method of claim 30 , wherein the capsule contains about 10 mg of the compound.
32. The method of claim 30 , wherein the capsule contains about 20 mg of the compound.
33. The method of claim 30 , wherein the capsule contains about 25 mg of the compound.
34. The method of claim 30 , wherein the capsule contains about 50 mg of the compound.
35. The method of claim 5 , wherein the crystal form is administered in the form of a tablet.
36. The method of claim 35 , wherein the tablet contains about 10 mg of the compound.
37. The method of claim 35 , wherein the tablet contains about 20 mg of the compound.
38. The method of claim 35 , wherein the tablet contains about 25 mg of the compound.
39. The method of claim 35 , wherein the tablet contains about 50 mg of the compound.