Crystalline Valbenazine Free Base

• US 20190315744A1
• Filed: 12/06/2017
• Published: 10/17/2019
• Est. Priority Date: 01/10/2017
• Status: Active Grant

• Current Assignee: Sandoz Ag (Novartis Ag)
• Original Assignee: Sandoz Ag (Novartis Ag)
• Inventors: Langes, Christoph, Reissmann, Stefan
• Granted Patent: US 10,703,750 B2
• Time in Patent Office: Days
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The present disclosure generally relates to crystalline valbenazine. The present disclosure also generally relates to a pharmaceutical composition comprising crystalline valbenazine, as well of methods of using crystalline valbenazine in the treatment of hyperkinetic disorders, and methods for obtaining such forms.

Claims

1. Crystalline valbenazine.

2. The crystalline valbenazine according to claim 1, in substantially pure form.

3. The crystalline valbenazine according to claim 1, characterized by a x-ray powder diffraction pattern comprising four or more 2θ

values selected from the group consisting of 6.0±

0.2°

, 6.8±

0.2°

, 8.4±

0.2°

, 10.0±

0.2°

, 14.2±

0.2°

, 17.6±

0.2°

, 18.2±

0.2° and

20.3±

0.2°

, when measured at a temperature of about 22°

C. using Cu Kα

radiation.

4. The crystalline valbenazine according to claim 3, having a X-ray diffraction spectrum substantially the same as the X-ray powder diffraction spectrum shown in FIG. 1.

5. The crystalline valbenazine according to claim 1 having a melting and/or decomposition temperature between 90°

C. and 95°

C.

6. A composition comprising at least 95 weight % of crystalline valbenazine according to claim 1, based the weight of the composition.

7. The composition of claim 6 consisting essentially of crystalline valbenazine characterized by a x-ray powder diffraction pattern comprising four or more 2θ

values selected from the group consisting of 6.0±

0.2°

, 6.8±

0.2°

, 8.4±

0.2°

, 10.0±

0.2°

, 14.2±

0.2°

, 17.6±

0.2°

, 18.2±

0.2° and

20.3±

0.2°

, when measured at a temperature of about 22°

C. using Cu Kα

radiation.

12. A process of making crystalline valbenazine according to claim 1, comprising:

allowing valbenazine to crystallize from a solvent comprising diethylether.

13. The process according to claim 12, wherein the solvent further comprises isopropyl alcohol, dichloromethane, methylethylketone, cyclohexanone, ethylacetate or cyclohexane.

14. The process according to claim 12, further comprising the step of carbon filtering.

15. The process according to claim 12, wherein valbenazine is allowed to crystallize at a temperature of from 0°

C. to 40°

C.

8-9. -9. (canceled)

10. A process of making a pharmaceutically acceptable acid addition salt of valbenazine, wherein

a) crystalline valbenazine free base is dissolved in a solvent,

b) the dissolved valbenazine free base is brought into contact with a pharmaceutically acceptable acid, and

c) a solid form of the pharmaceutically acceptable acid addition salt of valbenazine is allowed to form and isolated.

11. The process according to claim 10, wherein the solid form of the pharmaceutically acceptable acid addition salt of valbenazine is a crystalline solid form.