Crystalline forms of {[1-cyano-5-(4-chlorophenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-acetic acid
The present disclosure relates to crystalline forms of {[1-cyano-5-(4-chlorophenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-acetic acid (Compound A), the process of preparing crystalline forms of Compound A, the pharmaceutical compositions containing them, and the methods of use thereof.
1. Crystalline Form 1 of Compound A having the structure:
(Compound A, Form 1) characterized by having an X-ray powder diffractogram comprising a peak at 18.3°2θ±0.2°2θ, as determined on a diffractogram using Cu—Kα radiation.
2. Compound A, Form 1 of claim 1 , wherein the diffractogram further comprises at least one peak selected from 7.7, 11.2, 13.8, 14.7, 15.3, 15.8, 21.1, and 22.2°2θ±0.2°2θ, as determined on a diffractogram using Cu—Kα radiation.
3. Compound A, Form 1 of claim 1 , wherein the diffractogram further comprises a peak at 11.2±0.2°2θ.
4. Compound A, Form 1 of claim 3 , wherein the diffractogram further comprises peaks at 7.7, 13.8, 21.1 and 22.2°2θ±0.2°2θ.
5. Compound A, Form 1 of claim 4 , wherein the diffractogram is substantially as shown in FIG. 1 .
6. Compound A, Form 1 of claim 1 , characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 251° C.
7. Compound A, Form 1 of claim 6 , further comprising an exotherm at about 210° C.
8. Compound A, Form 1 of claim 7 , wherein the DSC curve is substantially as shown in FIG. 2 .
9. Compound A, Form 1 of claim 1 , characterized by a diffractogram which is substantially as shown in FIG. 1 , and by a DSC curve which is substantially as shown in FIG. 2 .
10. Crystalline Form 2 of Compound A having the structure:
(Compound A, Form 2), characterized by having an X-ray powder diffractogram comprising a peak at 19.3±0.2°2θ, as determined on a diffractogram using Cu—Kα radiation.
11. Compound A, Form 2 of claim 10 , wherein the diffractogram further comprises at least one peak selected from 8.1, 10.6, 11.5, 14.5, 16.2, 21.5, 21.9, 22.7, 24.5, and 26.6°2θ±0.2°2θ, as determined on a diffractogram using Cu—Kα radiation.
12. Compound A, Form 2 of claim 10 , wherein the diffractogram further comprises peaks at 10.6 and 11.5°2θ±0.2°2θ.
13. Compound A, Form 2 of claim 12 , wherein the diffractogram further comprises peaks at 14.5, 16.2, 24.5 and 26.6°2θ±0.2°2θ.
14. Compound A, Form 2 of claim 13 , wherein the diffractogram is substantially as shown in FIG. 3 .
15. Compound A, Form 2 of claim 10 , characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 249° C.
16. Compound A, Form 2 of claim 15 , wherein the DSC curve is substantially as shown in FIG. 4 .
17. Compound A, Form 2 of claim 10 , characterized by a diffractogram which is substantially as shown in FIG. 3 , and by a DSC curve which is substantially as shown in FIG. 4 .
18. A pharmaceutical composition comprising a crystalline form of Compound A having the structure:
wherein the crystalline form of Compound A comprises Form 1 characterized by having an X-ray powder diffractogram comprising a peak at 18.3°2θ±0.2°2θ, as determined on a diffractogram using Cu—Kα radiation, and at least one pharmaceutically acceptable excipient.
19. The pharmaceutical composition of claim 18 , wherein at least 95% of the crystalline form is Compound A, Form 1.
20. The pharmaceutical composition of claim 18 , wherein at least 99% of the crystalline form is Compound A, Form 1.
21. The pharmaceutical composition of claim 18 , wherein at least 99.9% of the crystalline form is Compound A, Form 1.
22. The pharmaceutical composition of claim 18 , wherein at least 99.99% of the crystalline form is Compound A, Form 1.
23. A pharmaceutical composition comprising a crystalline form of Compound A, having the structure:
wherein the crystalline form of Compound A comprises Form 2 characterized by having an X-ray powder diffractogram comprising a peak at 19.3±0.2°2θ, as determined on a diffractogram using Cu—Kα radiation, and at least one pharmaceutically acceptable excipient.
24. The pharmaceutical composition of claim 23 , wherein at least 95% of the crystalline form is Compound A, Form 2.
25. The pharmaceutical composition of claim 23 , wherein at least 99% of the crystalline form is Compound A, Form 2.
26. The pharmaceutical composition of claim 23 , wherein at least 99.9% of the crystalline form is Compound A, Form 2.
27. The pharmaceutical composition of claim 23 , wherein at least 99.99% of the crystalline form is Compound A, Form 2.
28. The pharmaceutical composition of claim 23 , wherein no more than 10% of the crystalline form is Compound A, Form 1, characterized by having an X-ray powder diffractogram comprising a peak at 18.3°2θ±0.2°2θ, as determined on a diffractogram using Cu—Kα radiation.
29. The pharmaceutical composition of claim 23 , wherein no more than 1% of the crystalline form is Compound A, Form 1, characterized by having an X-ray powder diffractogram comprising a peak at 18.3°2θ±0.2°2θ, as determined on a diffractogram using Cu—Kα radiation.
30. The pharmaceutical composition of claim 23 , wherein no more than 0.1% of the crystalline form is Compound A, Form 1, characterized by having an X-ray powder diffractogram comprising a leak at 18.3°2θ±0.2°2θ, as determined on a diffractogram using Cu—Kα radiation.
31. The pharmaceutical composition of claim 23 , wherein no more than 0.01% of the crystalline form is Compound A, Form 1, characterized by having an X-ray powder diffractogram comprising a peak at 18.3°2θ±0.2°2θ, as determined on a diffractogram using Cu—Kα radiation.
32. The pharmaceutical composition of claim 18 , wherein the composition is formulated for oral delivery.
33. The pharmaceutical composition of claim 18 , wherein the composition is formulated as a tablet or a capsule.
34. The pharmaceutical composition of claim 23 , wherein the composition is formulated for oral delivery.
35. The pharmaceutical composition of claim 23 , wherein the composition is formulated as a tablet or a capsule.
36. A method of treating, pretreating, or delaying onset of anemia, the method comprising administering to a patient a therapeutically effective amount of a composition of claim 18 .
37. A method of treating, pretreating, or delaying onset of anemia, the method comprising administering to a patient a therapeutically effective amount of a composition of claim 23 .
38. A process for making crystalline Form 1 of Compound A having the structure:
characterized by having an X-ray powder diffractogram comprising a peak at 18.3±0.2°2θ, as determined on a diffractogram using Cu—Kα radiation, comprising:
a) heating a mixture comprising a salt of Compound A optionally in the presence of a base;
b) cooling the mixture;
c) adding an acid to the mixture; and
d) isolating Form 1 of Compound A.
39. A process for making crystalline Form 2 of Compound A having the structure:
characterized by having an X-ray powder diffractogram comprising a peak at 19.3±0.2°2θ, as determined on a diffractogram using Cu—Kα radiation, comprising:
a) heating a mixture comprising a salt of Compound A;
b) adding an acid to the mixture and continuing heating;
c) cooling the mixture; and
d) isolating Form 2 of Compound A.