Solid forms comprising 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one and a coformer, compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9968627-B2
Application number	US-201414778553-A
Country	US
Kind code	B2
Filing date	Mar 25, 2014
Priority date	Mar 26, 2013
Publication date	May 15, 2018
Grant date	May 15, 2018

Abstract

Provided herein are solid forms comprising (a) 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one and (b) a coformer. Pharmaceutical compositions comprising the solid forms (e.g., cocrystals) and methods for treating, preventing and managing various disorders are also disclosed.

First claim

What is claimed is:

1. A solid form comprising (a) 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, prodrug, or clathrate thereof; and (b) a conformer selected from the group consisting of glycine, propyl gallate, and nicotinamide.

2. The solid form of claim 1 , wherein the molar ratio of 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one to the coformer is from about 2:1 to 1:2.

3. The solid of claim 2 , wherein the molar ratio of 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one to the coformer is about 1:1.

4. The solid form of claim 1 , which is crystalline.

5. The solid form of claim 1 , which is a cocrystal.

6. The solid form of claim 1 , which is greater than 80% by weight, greater than 90% by weight, greater than 95% by weight, greater than 97% by weight, or greater than 99% by weight a cocrystal.

7. The solid form of claim 1 , which is physically pure.

8. The solid form of claim 1 , which is free of other solid forms of 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one.

9. The solid form of claim 1 , which is free of solvent.

10. The solid form of claim 1 , which is free of water.

11. The solid form of claim 1 , further comprising amorphous 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one.

12. The solid form of claim 1 , which is stable.

13. The solid form of claim 1 , which is crystalline and thermally stable.

14. A pharmaceutical composition comprising the solid form of claim 1 .

15. The pharmaceutical composition of claim 14 , further comprising a pharmaceutically acceptable excipient or carrier.

16. The pharmaceutical composition of claim 14 , which is a single unit dosage form.

17. The pharmaceutical composition of claim 14 , which is a tablet.

18. The pharmaceutical composition of claim 14 , which is a capsule.

19. The pharmaceutical composition of claim 14 , wherein the 5-azacytidine is in an amount of from about 0.1 to about 5 mg.

20. A method of treating a disease comprising administering the solid form of claim 1 or the pharmaceutical composition of claim 14 to a subject wherein the disease is selected from the group consisting of multiple myeloma, myeloproliferative disease, anemia, scleroderma, and amyloidosis.

21. The method of claim 20 , further comprising administering a second active agent.

Assignees

• Celgene Corp

Inventors

• Stahly G Patrick
• Jonaitis David
• Hui Ho-Wah
• Klopfer Kevin J

Classifications

• A61K31/7052

  having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides · CPC title

• A61K9/145

  with organic compounds · CPC title

• C07H19/12

  Triazine radicals · CPC title

• A61K31/706 Primary

  containing six-membered rings with nitrogen as a ring hetero atom · CPC title

• A61P35/00

  Antineoplastic agents · CPC title