Solid state forms of Nilotinib salts
The present disclosure relates to solid state forms of Nilotinib fumarate and Nilotinib hydrochloride L-tartaric acid co-crystals, processes for preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
1. A crystalline form of Nilotinib fumarate designated as Form III, characterized by
an XRPD pattern having peaks at 5.5, 7.0, 11.0, 13.4 and 15.8 degrees two theta ±0.2 degrees two theta.
2. The crystalline Form III of Nilotinib fumarate according to claim 1 , further characterized by data selected from one or more of the following:
an FTIR spectrum having peaks at 3348, 1676, 1560, 1404 and 1296±4 cm −1 ; or
a Raman spectrum having peaks at 1668, 1614, 1407 and 1306±4 cm −1 ; or
a DSC endothermic peak of melting at about 228° C. (onset);
or combinations of these data.
3. The crystalline Form III of Nilotinib fumarate according to claim 1 , characterized by the XRPD pattern also having one, two, three, four, five, six or seven additional peaks selected from 14.0, 14.9, 16.3, 20.4, 20.5, 20.9 and 25.3 degrees two theta ±0.2 degrees two theta.
4. The crystalline Form III of Nilotinib fumarate according to claim 1 , wherein the crystalline form is an anhydrous form.
5. A solid pharmaceutical composition comprising a crystalline form according to claim 1 .
6. A solid pharmaceutical formulation comprising a crystalline form according to claim 1 and at least one pharmaceutically acceptable excipient.
7. A process for preparing the pharmaceutical formulation according to claim 6 , comprising combining the crystalline form according to claim 1 with the at least one pharmaceutically acceptable excipient.
8. A process for preparing Nilotinib base or a Nilotinib salt or a solid state form of Nilotinib base or a Nilotinib salt comprising preparing crystalline Form III of Nilotinib fumarate, and converting it to Nilotinib base or a Nilotinib salt or a solid state form of Nilotinib base or a Nilotinib salt.
9. The process of claim 8 , wherein the Nilotinib salt, or solid state form thereof, is Nilotinib hydrochloride or a solid state form thereof.
10. A crystalline form of Nilotinib fumarate designated as Form III, characterized by an XRPD pattern substantially as depicted in FIG. 1 .
11. A crystalline form of Nilotinib fumarate designated as Form III, characterized by a solid state 13 C NMR spectrum having characteristic peaks at 168.9, 159.1, 135.4 and 114.7±0.2 ppm.
12. A crystalline form of Nilotinib fumarate designated as Form III, characterized by a solid state 13 C NMR spectrum substantially as depicted in FIG. 4 .
13. A crystalline form of Nilotinib fumarate designated as Form III, characterized by a solid state 13 C NMR spectrum having the following chemical shift absolute differences from a peak at 119.0 ppm ±1 ppm of 49.9, 40.1, 16.4 and −4.3 ppm ±0.1 ppm.
14. A crystalline form of Nilotinib fumarate designated as Form III, characterized by a solid state 13 C NMR spectrum having chemical shift difference from a peak at 119.0 ppm ±1 ppm of 40.1 ppm ±0.1 ppm.
15. The crystalline Form III of Nilotinib fumarate according to claim 1 , further characterized by FTIR spectrum substantially as depicted in FIG. 5 .
16. The crystalline Form III of Nilotinib fumarate according to claim 1 , further characterized by a Raman spectrum substantially as depicted in FIG. 6 .
17. The crystalline Form III of Nilotinib fumarate according to claim 1 , further characterized by a DSC thermogram substantially as depicted in FIG. 7 .
18. The crystalline Form III of Nilotinib fumarate according to claim 1 , further characterized by a TGA thermogram substantially as depicted in FIG. 8 .