Solid forms of nilotinib hydrochloride

Patent metadata

Field	Value
Publication number	US-10016423-B2
Application number	US-201515518895-A
Country	US
Kind code	B2
Filing date	Oct 15, 2015
Priority date	Oct 16, 2014
Publication date	Jul 10, 2018
Grant date	Jul 10, 2018

Abstract

A solid form of Nilotinib hydrochloride, which exists as a co-crystal of nilotinib hydrochloride and levulinic acid having a molar ratio of nilotinib hydrochloride to levulinic acid of 1:2, and a process for the preparation of the co-crystal.

First claim

What is claimed is:

1. A co-crystal of Nilotinib hydrochloride and levulinic acid wherein the molar ratio of Nilotinib hydrochloride to levulinic acid is approximately 1:2.

2. The co-crystal of claim 1 , characterized by a powder x-ray diffraction (PXRD) diffractogram comprising a peak, expressed in degrees two-theta, at 9.5+/−0.2.

3. The co-crystal of claim 2 , further characterized by at least four peaks, expressed in degrees two-theta, selected from the group consisting of: 9.0+/−0.2, 10.4+/−0.2, 16.3+/−0.2, 18.2+/−0.2, 19.1+/−0.2, 21.8+/−0.2, 22.5+/−0.2, 22.7+/−0.2, 25.8+/−0.2 and 27.5+/−0.2.

4. The co-crystal of claim 1 , characterized by a PXRD diffractogram substantially similar to the PXRD diffractogram depicted in FIG. 1 .

5. The co-crystal of claim 1 , characterized by a DSC thermogram comprising an endothermic peak with a peak onset of approximately 144° C. and a peak maximum of about 146° C.

6. A process for the preparation of form APO-VII Nilotinib hydrochloride, the process comprising:
a) obtaining a solution comprising Nilotinib free base and levulinic acid;
b) treating the solution with hydrogen chloride thereby forming a mixture; and
c) isolating form APO-VII Nilotinib hydrochloride from the mixture.

7. The process of claim 6 , wherein the solution comprising Nilotinib free base and levulinic acid comprises an amount of levulinic acid with respect to Nilotinib free base of from about 3 volumes to about 6 volumes.

8. The process of claim 7 , wherein the solution comprising Nilotinib free base and levulinic acid comprises an amount of levulinic acid with respect to Nilotinib free base of about 4 volumes.

9. The process of claim 7 , wherein obtaining the solution comprises combining Nilotinib free base and levulinic acid thereby forming a combination and heating the combination to a temperature of between about 40° C. and about 90° C.

10. The process of claim 6 , wherein obtaining the solution comprises combining the Nilotinib free base and levulinic acid in the presence of an organic solvent selected from the group consisting of: alkyl esters, alkyl ethers, ketones and mixtures thereof.

11. The process of claim 10 , wherein the organic solvent is selected from the group consisting of: methyl t-butyl ether, tetrahydrofuran, ethyl acetate, isopropyl acetate, and mixtures thereof.

12. The process of claim 11 , wherein the organic solvent is ethyl acetate.

13. The process of claim 6 , wherein the treating the solution with hydrogen chloride comprises treating the solution with an aqueous solution of hydrogen chloride.

14. The process of claim 13 , wherein the mixture is combined with an organic solvent prior to isolating the form APO-VII Nilotinib hydrochloride.

15. The process of claim 14 , wherein the organic solvent combined with the mixture is selected from the group consisting of: methyl t-butyl ether, tetrahydrofuran, ethyl acetate, isopropyl acetate, and mixtures thereof.

16. The process of claim 14 , wherein the organic solvent combined with the mixture is ethyl acetate.

17. The process of claim 12 , wherein the amount of ethyl acetate with respect to Nilotinib free base is from about 2 volumes to about 8 volumes.

18. The process of claim 17 , wherein the amount of ethyl acetate with respect to Nilotinib free base is about 2 volumes.

19. The process of claim 6 , wherein the treating the solution with hydrogen chloride comprises treating the solution at a temperature of between about 40° C. and about 50° C.

Assignees

• Apotex Inc

Inventors

• Pompili Matthew
• Stradiotto David A
• Datta Probal Kanti

Classifications

• A61K47/542

  Carboxylic acids, e.g. a fatty acid or an amino acid · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• A61K31/506 Primary

  not condensed and containing further heterocyclic rings · CPC title

• C07C59/185

  Saturated compounds having only one carboxyl group and containing keto groups · CPC title