Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1- yl)methyl]-3-(trifluoromethyl)phenyl}benzamide and its mono hydrochloride salt
Novel crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide free base and 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride, pharmaceutical compositions thereof and methods of their preparation and use are disclosed herein.
1. Crystalline anhydrous ponatinib hydrochloride, characterized by an X-ray diffraction pattern comprising 2θ values (±0.3) at 5.9, 7.1, 12.5, 19.3, 23.8, and 26.1.
2. The crystalline anhydrous ponatinib hydrochloride of claim 1 , having a thermogravimetric analysis thermogram comprising a weight loss of no more than 1.0% w/w from about 30° C. to about 225° C.
3. The crystalline anhydrous ponatinib hydrochloride of claim 1 , having a differential scanning calorimetry thermogram comprising an endotherm with a maximum at 264.1° C.
4. A pharmaceutical composition comprising crystalline anhydrous ponatinib hydrochloride characterized by an X-ray diffraction pattern comprising 2θ values (±0.3) at 5.9, 7.1, 12.5, 19.3, 23.8, and 26.1 and a pharmaceutically acceptable carrier.
5. The pharmaceutical composition according to claim 4 , wherein the crystalline anhydrous ponatinib hydrochloride has a thermogravimetric analysis thermogram comprising a weight loss of no more than 1.0% w/w from about 30° C. to about 225° C.
6. The pharmaceutical composition according to claim 4 , wherein the crystalline anhydrous ponatinib hydrochloride has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at 264.1° C.
7. A method for treating chronic myeloid leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of crystalline anhydrous ponatinib hydrochloride characterized by an X-ray diffraction pattern comprising 2θ values (±0.3) at 5.9, 7.1, 12.5, 19.3, 23.8, and 26.1 or a pharmaceutical composition comprising the crystalline anhydrous ponatinib hydrochloride and a pharmaceutically acceptable carrier.
8. The method according to claim 7 , wherein the subject has chronic phase chronic myeloid leukemia.
9. The method according to claim 8 , wherein the subject has acute phase chronic myeloid leukemia.
10. The method according to claim 8 , wherein the subject has blast phase chronic myeloid leukemia.
11. The method according to claim 7 , wherein the subject has chronic phase, acute phase, or blast phase chronic myeloid leukemia with resistance or intolerance to at least one prior tyrosine-kinase inhibitor.
12. The method according to claim 7 , wherein the subject has chronic phase, acute phase, or blast phase chronic myeloid leukemia with resistance or intolerance to at least two prior tyrosine-kinase inhibitors.
13. The method according to claim 7 , wherein the leukemia results from a mutation in the Bcr-Abl kinase domain.
14. The method according to claim 7 , wherein the crystalline anhydrous ponatinib hydrochloride has a thermogravimetric analysis thermogram comprising a weight loss of no more than 1.0% w/w from about 30° C. to about 225° C.
15. The method according to claim 7 , wherein the crystalline anhydrous ponatinib hydrochloride has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at 264.1° C.
16. A method for treating Philadelphia chromosome positive acute lymphoblastic leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of crystalline form of ponatinib hydrochloride characterized by an X-ray diffraction pattern comprising 2θ values (±0.3) at 5.9, 7.1, 12.5, 19.3, 23.8, and 26.1 or a pharmaceutical composition comprising the crystalline anhydrous ponatinib hydrochloride and a pharmaceutically acceptable carrier.
17. The method of claim 16 , wherein the leukemia results from a mutation in the Bcr-Abl kinase domain.
18. The method according to claim 16 , wherein the crystalline anhydrous ponatinib hydrochloride has a thermogravimetric analysis thermogram comprising a weight loss of no more than 1.0% w/w from about 30° C. to about 225° C.
19. The method according to claim 16 , wherein the crystalline anhydrous ponatinib hydrochloride has a differential scanning calorimetry thermogram comprising an endotherm with a maximum at 264.1° C.