Crystal forms and production methods thereof

• US 10,377,708 B2
• Filed: 12/04/2018
• Issued: 08/13/2019
• Est. Priority Date: 12/05/2017
• Status: Active Grant

• Current Assignee: Sunovion Pharmaceuticals Inc. (Sumitomo Chemical Company Limited)
• Original Assignee: Sunovion Pharmaceuticals Inc. (Sumitomo Chemical Company Limited)
• Inventors: Snoonian, John R., Wilkinson, Harold Scott
• Primary Examiner(s): Anderson, Rebecca L
• Application Number:
  US16/209,263
• Publication Number:
  US 20190169123A1
• Time in Patent Office: 252 Days
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 207/09 Radicals substituted by nitrogen atoms, not forming part of a nitro radical

Abstract

The various aspects present inventions provide various crystalline forms of (S)-(−)-amisulpride, (R)-(+)-amisulpride, and solvates thereof and methods of making same. In various aspects, the inventions also provide methods of resolving racemic amisulpride.

Claims

1. A crystalline form of (R)-(+)-amisulpride characterized by a powder x-ray diffraction pattern comprising peaks, in terms of 2-theta, at 7.0±

0.20, 9.7±

0.2°

, and 15.4±

0.2°

.

2. The crystalline (R)-(+)-amisulpride of claim 1, further characterized by the powder x-ray diffraction pattern further comprising peaks, in terms of 2-theta, at 9.3±

0.2°

, and 19.4±

0.2°

.

3. The crystalline (R)-(+)-amisulpride of claim 2, further characterized by the powder x-ray diffraction pattern further comprising peaks, in terms of 2-theta, at 14.9±

0.2°

, 16.9±

0.2°

, and 20.1±

0.2°

.

4. The crystalline (R)-(+)-amisulpride of claim 3, further characterized by the powder x-ray diffraction pattern further comprising peaks, in terms of 2-theta, at 19.0±

0.20, 21.0±

0.2°

, and 23.2±

0.2°

.

5. The crystalline (R)-(+)-amisulpride of claim 1, characterized by a powder x-ray diffraction pattern substantially in accord with FIG.

6. The crystalline (R)-(+)-amisulpride of claim 1, characterized by having a melting point at about 102±

3°

C.

7. The crystalline (R)-(+)-amisulpride of claim 1, characterized by a differential scanning calorimetry thermogram comprising an endothermic event at 101±

3°

C.

8. The crystalline (R)-(+)-amisulpride of claim 1, having a differential scanning calorimetry thermogram substantially in accord with FIG. 2A.

20. A pharmaceutical composition comprising the crystalline form of claim 1 and a pharmaceutically acceptable carrier or diluent.

9. A crystalline form of (S)-(−

)-amisulpride characterized by a powder x-ray diffraction pattern comprising peaks, in terms of 2-theta, at 7.0±

0.2°

, 9.7±

0.2°

, and 15.4±

0.2°

.

10. The crystalline (S)-(−

)-amisulpride of claim 9, further characterized by the powder x-ray diffraction pattern further comprising peaks, in terms of 2-theta, at 9.3±

0.2°

, and 19.4±

0.2°

.

11. The crystalline (S)-(−

)-amisulpride of claim 10, further characterized by the powder x-ray diffraction pattern further comprising peaks, in terms of 2-theta, at 14.9±

0.2°

, 16.9±

0.2°

, and 20.2±

0.2°

.

12. The crystalline (S)-(−

)-amisulpride of claim 11, further characterized by the powder x-ray diffraction pattern further comprising peaks, in terms of 2-theta, at 19.1±

0.2°

, 21.0±

0.2°

, and 23.2±

0.2°

.

13. The crystalline (S)-(−

)-amisulpride of claim 9, characterized by a powder x-ray diffraction pattern substantially in accord with FIG. 3B.

14. The crystalline (S)-(−

)-amisulpride of claim 9 characterized by having a melting point at about 102±

3°

C.

15. The crystalline (S)-(−

)-amisulpride of claim 9, characterized by a differential scanning calorimetry thermogram comprising an endothermic event at 101±

3°

C.

16. The crystalline (S)-(−

)-amisulpride of claim 9, having a differential scanning calorimetry thermogram substantially in accord with FIG. 3A.

21. A pharmaceutical composition comprising the crystalline form of claim 9 and a pharmaceutically acceptable carrier or diluent.

17. A crystalline (R)-(+)-amisulpride or (S)-(−

)-amisulpride characterized by single crystal x-ray diffraction having a P1 space group and cell formula units (Z) of 4.

18. The crystalline form of (R)-(+)-amisulpride of claim 17, wherein the P1 space group has unit cell parameters:

a is about 12.3 Å

, b is about 12.8 Å

, c is about 14.1 Å

, α

is about 64.0°

, β

is about 73.4°

, and γ

is about 75.9.

19. The crystalline form of (S)-(−

)-amisulpride of claim 17, wherein the P1 space group has unit cell parameters;

a is about 12.4 Å

, b is about 12.8 Å

, c is about 14.1 Å

, α

is about 64.2°

, β

is about 73.6°

, and γ

is about 75.8°

.

22. A pharmaceutical composition comprising the crystalline form of claim 17 and a pharmaceutically acceptable carrier or diluent.