Crystalline polymorphs of the free base of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde
Disclosed are crystalline free base ansolvate forms of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde (or Compound 1), such as the free base Form I, Form II and Material N. Also disclosed are crystalline free base solvates of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde (or Compound 1).
1. A method for treating sickle cell disease, comprising administering to a patient in need thereof:
a composition comprising a crystalline ansolvate of Compound 1:
characterized by X-ray powder diffraction peaks (Cu Kα radiation) at 13.37°, 14.37°, 19.95° and 23.92° 2θ (each ±0.2° 2θ), wherein the composition is substantially free of other ansolvate polymorphs of Compound 1; and
another active agent.
2. The method of claim 1 , wherein the composition and the active agent are co-administered.
3. The method of claim 1 , wherein the composition and the active agent are administered in a single pharmaceutical composition.
4. The method of claim 1 , wherein the composition and the active agent are administered by the same route of administration.
5. The method of claim 1 , wherein the composition and the active agent are administered by different routes of administration.
6. The method of claim 1 , wherein the composition is administered orally.
7. The method of claim 4 , wherein the route of administration is oral.
8. The method of claim 1 , wherein the composition is substantially free of solvated polymorphs of Compound 1.
9. The method of claim 1 , wherein the composition comprises less than 10 mole % of amorphous forms of Compound 1.
10. A pharmaceutical composition comprising:
a composition comprising a crystalline ansolvate of Compound 1:
characterized by X-ray powder diffraction peaks (Cu Kα radiation) at 13.37°, 14.37°, 19.95° and 23.92° 2θ (each ±0.2° 2θ), wherein the composition is substantially free of other ansolvate polymorphs of Compound 1; and
another active agent.
11. The pharmaceutical composition of claim 10 , wherein the crystalline ansolvate of Compound 1 is characterized by an X-ray powder diffraction pattern (Cu Kα radiation) substantially similar to that of FIG. 5 .
12. The pharmaceutical composition of claim 10 , wherein the crystalline ansolvate of Compound 1 is characterized by an endothermic peak at 97±2° C. as measured by differential scanning calorimetry.
13. The pharmaceutical composition of claim 10 , wherein the composition is substantially free of solvated polymorphs of Compound 1.
14. The pharmaceutical composition of claim 10 , wherein the composition comprises less than 10 mole % of amorphous forms of Compound 1.