Pharmaceutical compositions comprising crystal forms of 5-azacytidine

1. A pharmaceutical composition for oral administration comprising crystalline Form I of 5-azacytidine substantially free of other forms of 5-azacytidine.

2. The pharmaceutical composition of claim 1 , which is in a single unit dosage form.

3. The pharmaceutical composition of claim 2 , which further comprises a carrier, diluent, or excipient.

4. The pharmaceutical composition of claim 3 , which comprises mannitol.

5. The pharmaceutical composition of claim 3 , which comprises microcrystalline cellulose.

6. The pharmaceutical composition of claim 3 , which comprises magnesium stearate.

7. The pharmaceutical composition of claim 3 , which is a tablet.

8. The pharmaceutical composition of claim 1 or 3 , which is a capsule.

9. The pharmaceutical composition of claim 3 , which contains between about 5 mg and about 200 mg of crystalline Form I of 5-azacytidine.

10. The pharmaceutical composition of claim 9 , which contains about 100 mg of crystalline Form I of 5-azacytidine.

11. A pharmaceutical composition for oral administration comprising crystalline Form I of 5-azacytidine substantially free of other forms of 5-azacytidine, wherein the crystalline Form I of 5-azacytidine is prepared according to a method comprising:

crystallizing 5-azacytidine from a solvent mixture comprising at least one polar aprotic solvent and at least one co-solvent, wherein the co-solvent is selected from:

1,1,2-trichloroethane,

1,2-dichloroethane,

1,2-dimethoxyethane,

1,4-dioxane,

1-butanol,

1-pentanol,

1-propanol,

2-butanol,

2-ethoxyethanol,

2-methoxyethanol,

2-methyl-1-propanol,

2-propanol (isopropyl alcohol),

3-methyl-1-butanol,

acetone,

acetonitrile,

anisole,

butyl acetate,

chlorobenzene,

cumene,

cyclohexane,

dichloromethane,

ethanol,

ethyl acetate,

ethyl ether,

ethyl formate,

ethyleneglycol,

formamide,

isobutyl acetate,

isopropyl acetate,

methyl acetate,

methylbutyl ketone,

methylcyclohexane,

methylethyl ketone,

methylisobutyl ketone,

N,N-dimethylacetamide,

N,N-dimethylformamide,

nitromethane,

propyl acetate,

pyridine,

sulfolane,

tert-butylmethyl ether,

tetrahydrofuran, and

tetralin; and

isolating the crystalline Form I of 5-azacytidine.

12. The pharmaceutical composition of claim 11 , wherein the method further comprises heating the solvent mixture to dissolve the 5-azacytidine.

13. The pharmaceutical composition of claim 11 , wherein the method further comprises cooling the solvent mixture to allow crystal formation.

14. The pharmaceutical composition of claim 11 , wherein the method further comprises seeding with crystalline Form I of 5-azacytidine.

15. The pharmaceutical composition of claim 11 , wherein the co-solvent is acetonitrile.

16. The pharmaceutical composition of claim 11 , wherein the co-solvent is ethanol.

17. The pharmaceutical composition of claim 11 , wherein the co-solvent is methylethyl ketone.

18. The pharmaceutical composition of claim 11 , wherein the co-solvent is 2-propanol (isopropanol).

19. The pharmaceutical composition of claim 11 , wherein the co-solvent is 1-propanol.

20. The pharmaceutical composition of claim 11 , wherein the polar aprotic solvent is selected from:

dimethylsulfoxide,

dimethylformamide,

dimethylacetamide, and

N-methylpyrrolidinone.

21. The pharmaceutical composition of claim 11 , wherein the polar aprotic solvent is dimethylsulfoxide.

22. The pharmaceutical composition of claim 11 , which is in a unit dosage form.

23. The pharmaceutical composition of claim 22 , which further comprises a carrier, diluent, or excipient.

24. The pharmaceutical composition of claim 23 , which comprises mannitol.

25. The pharmaceutical composition of claim 23 , which comprises microcrystalline cellulose.

26. The pharmaceutical composition of claim 23 , which comprises magnesium stearate.

27. The pharmaceutical composition of claim 23 , which is a tablet.

28. The pharmaceutical composition of claim 23 , which is a capsule.

29. The pharmaceutical composition of claim 23 , which contains between about 5 mg and about 200 mg of crystalline Form I of 5-azacytidine.

30. The pharmaceutical composition of claim 29 , which contains about 100 mg of crystalline Form I of 5-azacytidine.

31. A pharmaceutical composition for oral administration comprising crystalline Form I of 5-azacytidine substantially free of other forms of 5-azacytidine, wherein the crystalline Form I of 5-azacytidine is prepared according to a method comprising:

dissolving 5-azacytidine in dimethyl sulfoxide solvent;

seeding the dimethyl sulfoxide solution with crystalline Form I of 5-azacytidine;

adding methanol co-solvent during or after the seeding; and

isolating crystalline Form I of 5-azacytidine.

32. The pharmaceutical composition of claim 31 , which is in a unit dosage form.

33. The pharmaceutical composition of claim 32 , which further comprises a carrier, diluent, or excipient.

34. The pharmaceutical composition of claim 33 , which comprises mannitol.

35. The pharmaceutical composition of claim 33 , which comprises microcrystalline cellulose.

36. The pharmaceutical composition of claim 33 , which comprises magnesium stearate.

37. The pharmaceutical composition of claim 33 , which is a tablet.

38. The pharmaceutical composition of claim 33 , which is a capsule.

39. The pharmaceutical composition of claim 33 , which contains between about 5 mg and about 200 mg of crystalline Form I of 5-azacytidine.

40. The pharmaceutical composition of claim 39 , which contains about 100 mg of crystalline Form I of 5-azacytidine.