Crystalline form of Valbenazine dibesylate

Patent metadata

Field	Value
Publication number	US-11220500-B2
Application number	US-201916718841-A
Country	US
Kind code	B2
Filing date	Dec 18, 2019
Priority date	Dec 27, 2018
Publication date	Jan 11, 2022
Grant date	Jan 11, 2022

Abstract

The present invention provides a novel crystalline form of Valbenazine dibesylate, Valbenazine dibesylate Form APO-I, compositions and processes for the preparation thereof, and the use of this crystalline form in the treatment of hyperkinetic disorders, including tardive dyskinesia.

First claim

What is claimed is:

1. A crystalline form of Valbenazine dibesylate characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.3°, 9.8° and 15.6°.

2. The crystalline form of claim 1 , characterized by a PXRD diffractogram further comprising at least three peaks, expressed in degrees 2θ (±0.2°), selected from the group consisting of: 5.3°, 7.7°, 8.5°, 12.5°, 14.0°, 16.8°, 17.1°, 17.8°, 18.6° and 19.7°.

3. The crystalline form of claim 1 , characterized by a PXRD diffractogram further comprising peaks, expressed in degrees 2θ (±0.2°), at 5.3°, 7.7°, 8.5°, 12.5°, 14.0°, 16.8°, 17.1°, 17.8°, 18.6° and 19.7°.

4. The crystalline form of claim 1 , characterized by a DSC thermogram comprising an endothermic peak with a peak onset of approximately 235° C. and a peak maximum of approximately 238° C.

5. The crystalline form of claim 1 , characterized by a DSC thermogram that is substantially the same in appearance as the DSC thermogram provided in FIG. 2 .

6. The crystalline form of claim 1 , providing a PXRD diffractogram comprising peaks in substantially the same positions (±0.2° 2 θ) as those shown in FIG. 1 .

7. A pharmaceutical composition comprising the crystalline form of Valbenazine dibesylate according to claim 2 , and one or more pharmaceutically acceptable excipients.

8. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition is a capsule.

9. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition comprises an amount of the crystalline form that is equivalent to 40 mg or 80 mg Valbenazine free base.

10. A process for the preparation of the crystalline form of Valbenazine dibesylate according to claim 1 , the process comprising:
(i) reacting, in the presence of a first solvent (S1), a compound of Formula (2):

with at least two equivalents of benzenesulfonic acid to afford Valbenazine dibesylate;
(ii) forming a suspension by crystallization of the Valbenazine dibesylate; and
(iii) filtering the suspension to isolate the crystalline Valbenazine dibesylate,
wherein P is an acid-labile protecting group, wherein P is tert-butoxycarbonyl.

11. The process of claim 10 , wherein the first solvent (S1) is selected from the group consisting of nitriles and halogenated hydrocarbons.

12. The process of claim 11 , wherein the first solvent (S1) is acetonitrile or dichloromethane.

13. The process of claim 10 , wherein the suspension of crystalline Valbenazine dibesylate in step (ii) is formed by the addition of a second solvent (S2).

14. The process of claim 13 , wherein the second solvent (S2) is butanone.

15. The process of claim 13 , wherein the first solvent (S1) is partially or wholly removed prior to addition of the second solvent (S2).

16. The crystalline form of claim 2 , characterized by a DSC thermogram comprising an endothermic peak with a peak onset of approximately 235° C. and a peak maximum of approximately 238° C.

17. The crystalline form of claim 2 , characterized by a DSC thermogram that is substantially the same in appearance as the DSC thermogram provided in FIG. 2 .

18. The crystalline form of claim 5 , providing a PXRD diffractogram comprising peaks in substantially the same positions (±0.2° 2 θ) as those shown in FIG. 1 .

Assignees

• Apotex Inc

Inventors

• Raheem Mohammed Abdul
• Zhao Yajun
• Nguyen Minh T N
• Zaki Mohamed Ibrahim
• Gerster Jenny L
• Green Stuart P
• Rey Allan W

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title