Solid state forms of Nilotinib salts

Patent metadata

Field	Value
Publication number	US-10640487-B2
Application number	US-201716084357-A
Country	US
Kind code	B2
Filing date	Mar 13, 2017
Priority date	Mar 14, 2016
Publication date	May 5, 2020
Grant date	May 5, 2020

Abstract

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.

First claim

The invention claimed is:

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 .

Assignees

• Teva Pharma

Inventors

• Ceric Helena
• Avdejev Igor
• Topic Edi

Classifications

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P35/00

  Antineoplastic agents · CPC title