Crystalline forms of benzoquinoline inhibitors of vesicular monoamine transporter 2

Patent metadata

Field	Value
Publication number	US-10632107-B2
Application number	US-201916410248-A
Country	US
Kind code	B2
Filing date	May 13, 2019
Priority date	May 14, 2018
Publication date	Apr 28, 2020
Grant date	Apr 28, 2020

Abstract

The present invention provides crystalline forms of Deutetrabenazine. Specific crystalline forms provided by the present invention include Deutetrabenazine Form APO-I, a co-crystal of Deutetrabenazine and quercetin, and Deutetrabenazine Form APO-II, a co-crystal of Deutetrabenazine and luteolin. Also provided are pharmaceutical compositions including the Deutetrabenazine crystalline forms, and the use of these forms in the treatment of tardive dyskinesia and chorea associated with Huntington's disease.

First claim

What is claimed is:

1. A crystalline form of Deutetrabenazine and quercetin characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.2°, 9.3° and 14.1°.

2. The crystalline form of claim 1 , wherein the molar ratio of Deutetrabenazine to quercetin is 1:1.

3. The crystalline form of claim 1 , further comprising at least three peaks, expressed in degrees 2θ (±0.2°), selected from the group consisting of: 6.9°, 10.3°, 11.1°, 12.4°, 15.7° and 18.6°.

4. The crystalline form of claim 1 , further comprising peaks, expressed in degrees 2θ (±0.2°), at 6.9°, 10.3°, 11.1°, 12.4°, 15.7° and 18.6°.

5. The crystalline form of claim 1 providing a PXRD diffractogram substantially the same in appearance as the PXRD diffractogram provided in FIG. 1 .

6. A crystalline form of Deutetrabenazine and luteolin, characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°) at 6.2°, 9.3° and 14.2°.

7. The crystalline form of claim 6 , wherein the molar ratio of Deutetrabenazine to luteolin is 1:1.

8. The crystalline form of claim 6 , further comprising at least three peaks, expressed in degrees 2θ (±0.2°), selected from the group consisting of: 6.9°, 10.3°, 11.1°, 12.4°, 15.7° and 18.6°.

9. The crystalline form of claim 6 , further comprising peaks, expressed in degrees 2θ (±0.2°), at 6.9°, 10.3°, 11.1°, 12.4°, 15.7° and 18.6°.

10. The crystalline form of claim 6 providing a PXRD diffractogram substantially the same in appearance as the PXRD diffractogram provided in FIG. 2 .

11. A pharmaceutical composition comprising a crystalline form of Deutetrabenazine and quercetin or luteolin and one or more pharmaceutically acceptable excipients, wherein:
the crystalline form of Deutetrabenazine and quercetin is characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.2°, 9.3° and 14.1°; and
the crystalline form of Deutetrabenazine and luteolin is characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.2°, 9.3° and 14.2° .

12. The pharmaceutical composition of claim 11 comprising a crystalline form of Deutetrabenazine and quercetin characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.2°, 9.3° and 14.1°.

13. The pharmaceutical composition of claim 11 comprising a crystalline form of Deutetrabenazine and luteolin characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.2°, 9.3° and 14.2°.

14. The pharmaceutical composition of claim 11 , wherein the pharmaceutical composition is a tablet.

15. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition is a tablet.

16. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition is a tablet.

Assignees

• Apotex Inc

Inventors

• Souza Fabio E S
• Khalili Bahareh
• Rey Allan W

Classifications

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K31/353 Primary

  3,4-Dihydrobenzopyrans, e.g. chroman, catechin · CPC title

• A61K31/4375 Primary

  the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine · CPC title