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-methyi-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyljbenzamide free base and 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyi-N-{4-[(4-methyl piperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride, pharmaceutical compositions thereof and methods of their preparation and use are disclosed herein. The instant application is directed to novel crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyi-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl}phenyl}benzamide and 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyi-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride, compositions comprising such crystalline forms, and to methods of their preparation and use.
1. Crystalline Form A of ponatinib hydrochloride characterized by an x-ray powder diffraction pattern comprising at least five 2θ values (±0.3) chosen from 5.9, 7.1, 10.0, 12.5, 16.4, 19.3, 21.8, 23.8, and 26.1.
2. Crystalline ponatinib hydrochloride of which more than 90% is the crystalline Form A of ponatinib hydrochloride of claim 1 .
3. The crystalline Form A of ponatinib hydrochloride of claim 1 characterized by an x-ray powder diffraction pattern substantially as shown in FIG. 4 .
4. Crystalline Form A ponatinib hydrochloride characterized by an x-ray powder diffraction pattern comprising at least five 2θ values (±0.3) chosen from 5.9, 7.1, 10.0, 12.5, 13.6, 14.1, 15.0, 16.4, 17.7, 18.6, 19.3, 20.4, 21.8, 22.3, 23.8, 24.9, 26.1, 27.0, 28.4, 30.3, 31.7, and 35.1.
5. A pharmaceutical composition comprising crystalline Form A ponatinib hydrochloride according to claim 1 and at least one pharmaceutically acceptable carrier, vehicle or excipient.
6. A pharmaceutical composition comprising crystalline Form A ponatinib hydrochloride according to claim 2 and at least one pharmaceutically acceptable carrier, vehicle or excipient.
7. A pharmaceutical composition consisting essentially of the crystalline Form A of ponatinib hydrochloride of claim 1 .
8. A method for treating chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of claim 5 .
9. A method for treating chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of claim 6 .
10. A pharmaceutical composition comprising crystalline Form A ponatinib hydrochloride according to claim 3 and at least one pharmaceutically acceptable carrier, vehicle or excipient.
11. A method for treating chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of claim 10 .
12. Crystalline ponatinib hydrochloride of which more than 90% is the crystalline Form A of ponatinib hydrochloride of claim 4 .
13. A pharmaceutical composition comprising crystalline Form A ponatinib hydrochloride according to claim 4 and at least one pharmaceutically acceptable carrier, vehicle or excipient.
14. A pharmaceutical composition comprising crystalline Form A ponatinib hydrochloride according to claim 12 and at least one pharmaceutically acceptable carrier, vehicle or excipient.
15. A pharmaceutical composition consisting essentially of the crystalline Form A of ponatinib hydrochloride of claim 4 .
16. A method for treating chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of claim 13 .
17. A method for treating chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of claim 14 .