Solid forms of nilotinib hydrochloride

Patent metadata

Field	Value
Publication number	US-9376419-B2
Application number	US-201314436049-A
Country	US
Kind code	B2
Filing date	Oct 15, 2013
Priority date	Oct 15, 2012
Publication date	Jun 28, 2016
Grant date	Jun 28, 2016

Abstract

Disclosed are solid forms of Nilotinib hydrochloride and methods of preparation of various crystalline solvates of Nilotinib HCl including benzyl alcohol, acetic acid, propylene glycol, and isopropanol. Nilotinib HCl is a tyrosine kinase inhibitor used for the treatment of drug resistant chronic myelogenous leukemia (CML).

First claim

What is claimed is:

1. A crystalline solid form of Nilotinib hydrochloride having an X-ray powder diffraction pattern comprising peaks, in terms of degrees 2 -theta, at approximately 6.0, 6.5, 18.1, 19.5, 20.8 and 25.3.

2. The crystalline solid form of Nilotinib hydrochloride of claim 1 having an X-ray powder diffraction pattern as shown in FIG. 1 .

3. The crystalline solid form of Nilotinib hydrochloride of claim 1 wherein the crystalline solid form of Nilotinib hydrochloride is a benzyl alcohol solvate wherein the molar ratio of Nilotinib hydrochloride to benzyl alcohol is approximately 1:1.

4. A crystalline solid form of Nilotinib hydrochloride having an X-ray powder diffraction pattern comprising peaks, in terms of degrees 2 -theta, at approximately 7.5, 9.1, 11.0, 19.6, 20.8, 21.8, and 24.1.

5. The crystalline solid form of Nilotinib hydrochloride of claim 4 having an X-ray powder diffraction pattern as shown in FIG. 2 .

6. The crystalline solid form of Nilotinib hydrochloride of claim 4 having a differential scanning calorimetry thermogram comprising an endothermic peak with an onset temperature of approximately 134° C.

7. The crystalline solid form of Nilotinib hydrochloride of claim 4 having a differential scanning calorimetry thermogram as shown in FIG. 3 .

8. The crystalline solid form of Nilotinib hydrochloride of claim 4 wherein the crystalline solid form of Nilotinib hydrochloride is a propylene glycol solvate wherein the molar ratio of propylene glycol to Nilotinib hydrochloride is approximately 1:1.

9. A crystalline solid form of Nilotinib hydrochloride having an X-ray powder diffraction pattern comprising peaks, in terms of degrees 2 -theta, at approximately 6.2, 12.5, 18.8, 22.0, 24.0, and 26.0.

10. The crystalline solid form of Nilotinib hydrochloride of claim 9 having an X-ray powder diffraction pattern as shown in FIG. 4 .

11. The crystalline solid form of Nilotinib hydrochloride of claim 9 wherein crystalline solid form of Nilotinib hydrochloride comprises acetic acid salt wherein the molar ratio of acetic acid to Nilotinib hydrochloride is approximately 2:1.

12. A crystalline solid form of Nilotinib hydrochloride having an X-ray powder diffraction pattern comprising peaks, in terms of degrees 2 -theta, at approximately 6.8, 9.2, 13.1, 13.9, 17.9 and 25.3.

13. The crystalline solid form of Nilotinib hydrochloride of claim 12 having an X-ray powder diffraction pattern as shown in FIG. 5 .

14. The crystalline solid form of Nilotinib hydrochloride of claim 12 having a differential scanning calorimetry thermogram comprising an endothermic peak with an onset temperature of approximately 210° C.

15. The crystalline solid form of Nilotinib hydrochloride of claim 12 having a differential scanning calorimetry thermogram as shown in FIG. 6 .

16. A crystalline solid form of Nilotinib hydrochloride having an X-ray powder diffraction pattern comprising peaks, in terms of degrees 2 -theta, at approximately 7.2, 9.6, 16.0, 17.6, 21.8, and 26.0.

17. The crystalline solid form of Nilotinib hydrochloride of claim 16 having an X-ray powder diffraction pattern as shown in FIG. 7 .

18. The crystalline solid form of Nilotinib hydrochloride of claim 16 wherein the crystalline solid form of Nilotinib hydrochloride comprises acetic acid salt wherein the molar ratio of acetic acid to Nilotinib hydrochloride is approximately 1:1.

Assignees

• Apotex Inc

Inventors

• Datta Probal Kanti
• Zetina-Rocha Carlos
• Mcphail Cameron L
• Zhao Yajun
• Weeratunga Gamini

Classifications

• A61P35/02

  specific for leukemia · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title