Solid forms comprising 4-amino-i-b-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-2016296546-A1
Application number	US-201414778553-A
Country	US
Kind code	A1
Filing date	Mar 25, 2014
Priority date	Mar 26, 2013
Publication date	Oct 13, 2016
Grant date	—

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 coformer.

2 . The solid form of claim 1 , wherein the coformer is mandelic acid, glycine, glycolic acid, malonic acid, gallic acid, maleic acid, nicotinamide, cyclamic acid, ketoglutaric acid, propyl gallate or zinc chloride.

3 . The solid form of claim 2 , wherein the coformer is mandelic acid

4 . The solid form of claim 2 , wherein the coformer is glycine.

5 . The solid form of claim 2 , wherein the coformer is glycolic acid

6 . The solid form of claim 2 , wherein the coformer is malonic acid.

7 . The solid form of claim 2 , wherein the coformer is propyl gallate.

8 . The solid form of claim 2 , wherein the coformer is cyclamic acid.

9 . The solid form of claim 2 , wherein the coformer is nicotinamide.

10 . The solid form of claim 2 , wherein the coformer is maleic acid.

11 . The solid form of claim 2 , wherein the coformer is zinc chloride.

12 . The solid form of claim 2 , wherein the coformer is gallic acid.

13 . The solid form of claim 2 , wherein the coformer is ketoglutaric acid.

14 . The solid form of any one of claims 1 - 13 , 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.

15 . The solid of claim 14 , 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

16 . The solid form of any one of claims 1 - 15 , which is substantially crystalline.

17 . The solid form of any one of claims 1 - 16 , which is substantially a cocrystal.

18 . The solid form of any one of claims 1 - 17 , 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.

19 . The solid form of any one of claims 1 - 18 , which is substantially physically pure.

20 . The solid form of any one of claims 1 - 19 , which is substantially free of other solid forms of 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one.

21 . The solid form of any one of claims 1 - 20 , which is substantially free of solvent.

22 . The solid form of any one of claims 1 - 21 , which is substantially free of water.

23 . The solid form of any one of claims 1 - 22 , further comprising amorphous 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one.

24 . The solid form of any one of claims 1 - 23 , which is stable.

25 . The solid form of any one of claims 1 - 24 , which is substantially crystalline and thermally stable.

26 . A pharmaceutical composition comprising the solid form of any one of claims 1 - 25 .

27 . The pharmaceutical composition of claim 26 , further comprising a pharmaceutically acceptable excipient or carrier.

28 . The pharmaceutical composition of claim 26 or claim 27 , which is a single unit dosage form.

29 . The pharmaceutical composition of any one of claims 26 - 28 , which is a tablet.

30 . The pharmaceutical composition of any one of claims 26 - 28 , which is a capsule.

31 . The pharmaceutical composition of any one of claims 26 - 30 , wherein the 5-azacytidine is in an amount of from about 0.1 to about 5 mg.

32 . A method of treating a disease, comprising administering the solid form of any one of claims 1 - 13 or the pharmaceutical composition of any one of claims 26 - 30 to a subject in need thereof

33 . The method of claim 32 , wherein the disease is multiple myeloma.

34 . The method of claim 32 , wherein the disease is myeloproliferative disease.

35 . The method of claim 32 , wherein the disease is anemia.

36 . The method of claim 32 , wherein the disease is scleroderma.

37 . The method of claim 32 , wherein the disease is amyloidosis.

38 . The method of any one of claims 32 - 337 , 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

• A61K31/7064

  containing condensed or non-condensed pyrimidines · CPC title

• A61K9/145

  with organic compounds · CPC title

• A61K31/706 Primary

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

• C07H19/12

  Triazine radicals · CPC title