Crystalline Form Of Nicotinamide Riboside

• US 20170210774A1
• Filed: 07/24/2015
• Published: 07/27/2017
• Est. Priority Date: 07/24/2014
• Status: Active Grant

• Current Assignee: W R Grace & Company - CONN (WR Grace & Company)
• Original Assignee: W R Grace & Company - CONN (WR Grace & Company)
• Inventors: Carlson, Erik C., Standen, Michael C., Morrill, Westin M.
• Granted Patent: US 10,323,058 B2
• Time in Patent Office: Days
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07H 19/048 Pyridine radicals

Abstract

Provided are crystalline forms of nicotinamide riboside, including a Form I of nicotinamide riboside chloride according to formula (I). Also disclosed are pharmaceutical compositions comprising the crystalline Form I of nicotinamide riboside chloride, and methods of producing such pharmaceutical compositions. In other aspects, the present disclosure pertains to methods comprising administering to a subject the crystalline Form I of nicotinamide riboside chloride. The present disclosure also provides methods of preparing the crystalline Form I of nicotinamide riboside chloride. Also provided are a crystalline Form I of nicotinamide riboside chloride that is prepared according to any of the disclosed methods for preparing the crystalline Form I.

Claims

1. A crystalline Form I of nicotinamide riboside chloride according to formula I

2. The crystalline Form I according to claim 1 that is characterized by a powder X-ray diffraction pattern having peaks at 5.1, 15.7, and 21.7 degrees two theta ±

0.2 degrees two theta.

5. The crystalline Form I according to any preceding claim that is characterized by a powder X-ray diffraction pattern substantially as shown in FIG. 1.

6. The crystalline Form I according to claim 1 that is characterized by a powder X-ray diffraction pattern having peaks substantially as shown in Table 1±

0.2 degrees two theta.

7. The crystalline Form I according to claim 1 that is characterized by an IR spectrum having peaks at 671.7, 1035.6, and 1061.8 cm⁻

1±

0.2 cm<sup>−

1</sup>.

8. The crystalline Form I according to claim 1 that is characterized by an IR spectrum substantially as shown in FIG. 2.

9. The crystalline Form I according to claim 1 that is characterized by an IR spectrum having peaks substantially as shown in Table 2±

0.2 cm<sup>−

1</sup>.

10. The crystalline Form I according to claim 1 that is further characterized by a DSC thermogram substantially as shown in FIG. 4.

11. The crystalline Form I according to claim 1 that is further characterized by a DSC thermogram obtained using a heating rate of 10 K/min comprising an endothermic event with an onset temperature of 119°

C.±

2°

C., an endothermic event with a peak temperature of 123°

C.±

2°

C., or both.

12. The crystalline Form I according to claim 1 that is further characterized by a DSC thermogram obtained using a heating rate of 1 K/min comprising an endothermic event with an onset temperature of 104°

C.±

2°

C., a peak temperature of 108°

C.±

2°

C., or both.

13. The crystalline Form I according to claim 1 that is further characterized by a DSC thermogram obtained using a heating rate of 2 K/min comprising an endothermic event with an onset temperature of 109°

C.±

2°

C., a peak temperature of 113°

C.±

2°

C., or both.

14. The crystalline Form I according to claim 1 that is further characterized by a DSC thermogram obtained using a heating rate of 5 K/min comprising an endothermic event with an onset temperature of 114°

C.±

2°

C., a peak temperature of 118°

C.±

2°

C., or both.

15. The crystalline Form I according to claim 1 that is further characterized by a DSC thermogram obtained using a heating rate of 20 K/min comprising an endothermic event with an onset temperature of 122°

C.±

2°

C., a peak temperature of 128°

C.±

2°

C., or both.

16. The crystalline Form I according to claim 1 that is further characterized by a TGA/SDTA thermogram substantially as shown in FIG. 7A.

17. The crystalline Form I according to claim 1 that is further characterized by a TGA/SDTA thermogram comprising an endothermic event at 116°

C.±

2°

C. and a mass loss of about 0.4%.

18. The crystalline Form I according to claim 1 that is further characterized by a DVS change in mass plot substantially as shown in FIG. 8A.

19. The crystalline Form I according to claim 1 that is further characterized by a DVS isotherm plot substantially as shown in FIG. 8B.

20. The crystalline Form I according to claim 1 that is further characterized by a water vapor sorption isotherm showing a water uptake of not more than about 0.5 wt % at a relative humidity of up to 60%.

21. The crystalline Form I according to claim 1 that is further characterized by a water vapor sorption isotherm showing a water uptake of not more than about 1.0 wt %, at a relative humidity of up to 70%.

22. The crystalline Form I according to claim 1 wherein said crystalline Form I is anhydrous.

25. A method comprising administering to a subject the crystalline Form I according to claim 1.

26. The method according to claim 25 wherein said crystalline Form I is administered to said subject in a composition that further comprises a pharmaceutically acceptable excipient.

3-4. -4. (canceled)

23-24. -24. (canceled)

27-32. -32. (canceled)