Crystalline forms of Ponatinib hydrochloride
The present invention provides novel crystalline forms of Ponatinib hydrochloride. Specific crystalline forms provided by the present invention include Ponatinib hydrochloride Form APO-I, APO-III and APO-IV, each of which is obtained from acetonitrile/formic acid solutions. Additionally, Form APO-V is provided, which is obtained from concentrated hydrochloric acid.
1. A crystalline form of Ponatinib hydrochloride, characterized by a powder X-ray diffraction (PXRD) diffractogram comprising peaks, expressed in degrees 2θ (±) 0.2°, at 7.7°, 9.2°, 11.2° and 17.5°.
2. The crystalline form of claim 1 , characterized by a PXRD diffractogram further comprising at least two peaks, expressed in degrees 2θ (±0.2°), selected from the group consisting of 13.5°, 14.4°, 14.9°, 16.5°, 17.5° and 22.9°.
3. The crystalline form of claim 1 , characterized by a PXRD diffractogram further comprising peaks, expressed in degrees 2θ (±0.2°), at 13.5°, 14.4°, 14.9°, 16.5°, 17.5° and 22.9°.
4. The crystalline form of claim 2 , having a weight percentage of water of between approximately 2.7 wt % and 4.1 wt %.
5. The crystalline form of claim 1 , providing a PXRD diffractogram comprising peaks in substantially the same positions (approximately ±0.2° 2θ) as those shown in FIG. 3 .
6. A crystalline form of Ponatinib hydrochloride, characterized by a powder X-ray diffraction (PXRD) diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 8.8°, 9.6° and 13.2°.
7. The crystalline form of claim 6 , characterized by a PXRD diffractogram further comprising peaks, expressed in degrees 2θ (±0.2°), at 14.4° and 23.0°.
8. The crystalline form of claim 6 , characterized by a PXRD diffractogram further comprising peaks, expressed in degrees 2θ (±0.2°), at 14.4°, 16.5°, 18.7°, 19.2° and 23.0°.
9. The crystalline form of claim 6 , having a weight percentage of formic acid of at least approximately 3.9 wt %.
10. The crystalline form of claim 6 , having a weight percentage of formic acid of between approximately 3.9 wt % and approximately 7.5 wt %.
11. The crystalline form of claim 6 , having a molar ratio of Ponatinib hydrochloride to formic acid of between approximately 1:0.5 and approximately 1:1.
12. The crystalline form of claim 6 , providing a PXRD diffractogram comprising peaks in substantially the same positions (approximately ±0.2° 2θ) as those shown in FIG. 1 .
13. A pharmaceutical composition comprising the crystalline form of Ponatinib hydrochloride of claim 1 , and one or more pharmaceutically acceptable excipients.
14. The crystalline form of claim 3 , having a weight percentage of water of between approximately 2.7 wt % and 4.1 wt %.
15. The crystalline form of claim 2 , providing a PXRD diffractogram comprising peaks in substantially the same positions (approximately ±0.2° 2θ) as those shown in FIG. 3 .
16. The crystalline form of claim 3 , providing a PXRD diffractogram comprising peaks in substantially the same positions (approximately ±0.2° 2θ) as those shown in FIG. 3 .