Pharmaceutical compositions comprising 5-azacytidine monohydrate
Provided herein are pharmaceutical compositions or dosage forms comprising crystalline 5-azacytidine monohydrate. The pharmaceutical compositions or dosage forms provided herein may be used for oral administration in the treatment of diseases, including the treatment of myelodysplastic syndromes (MDS).
1. A solid pharmaceutical composition for oral administration comprising crystalline 5-azacytidine monohydrate substantially free of other solid forms of 5-azacytidine, and a pharmaceutically acceptable carrier, diluent, or excipient; wherein the composition is a capsule or a tablet, wherein the crystalline 5-azacytidine monohydrate is characterized by X-Ray Powder Diffraction peaks at the following approximate positions:
2θ Angle (degree)
6.566
11.983
13.089
15.138
17.446
20.762
21.049
22.776
24.363
25.743
26.305
28.741
31.393
32.806
33.043
33.536
36.371
39.157
41.643,
and wherein the composition contains between about 5 mg and about 200 mg of 5-azacytidine.
2. The pharmaceutical composition of claim 1 , which is in a single unit dosage form.
3. The pharmaceutical composition of claim 1 , which is a tablet.
4. The pharmaceutical composition of claim 1 , which is a capsule.
5. The pharmaceutical composition of claim 1 , which contains about 100 mg of 5-azacytidine.
6. The pharmaceutical composition of claim 1 , which comprises at least one of mannitol, microcrystalline cellulose, and magnesium stearate.
7. The pharmaceutical composition of claim 1 , wherein the crystalline 5-azacytidine monohydrate is prepared according to a method comprising:
contacting solid 5-azacytidine with water for at least about 19 hours; and
isolating crystalline 5-azacytidine monohydrate.
8. The pharmaceutical composition of claim 7 , wherein the solid 5-azacytidine comprises at least one of Form I, Form II, Form IV, Form V, Form VI, Form VII, or Form VIII of 5-azacytidine.
9. The pharmaceutical composition of claim 8 , wherein the solid 5-azacytidine comprises Form I of 5-azacytidine.
10. The pharmaceutical composition of claim 8 , wherein the solid 5-azacytidine comprises Form I and Form II of 5-azacytidine.
11. The pharmaceutical composition of claim 8 , wherein the solid 5-azacytidine comprises Form IV of 5-azacytidine.
12. The pharmaceutical composition of claim 8 , wherein the solid 5-azacytidine comprises Form V of 5-azacytidine.
13. The pharmaceutical composition of claim 8 , wherein the solid 5-azacytidine comprises Form VI of 5-azacytidine.
14. The pharmaceutical composition of claim 8 , wherein the solid 5-azacytidine comprises Form I and Form VI of 5-azacytidine.
15. The pharmaceutical composition of claim 8 , wherein the solid 5-azacytidine comprises Form I and Form VII of 5-azacytidine.
16. The pharmaceutical composition of claim 8 , wherein the solid 5-azacytidine comprises Form VIII of 5-azacytidine.
17. A solid pharmaceutical composition for oral administration comprising crystalline 5-azacytidine monohydrate substantially free of other solid forms of 5-azacytidine, and a pharmaceutically acceptable carrier, diluent, or excipient; wherein the composition is a capsule or a tablet, wherein the crystalline 5-azacytidine monohydrate is characterized by an X-ray powder diffraction pattern corresponding to the representative X-ray powder diffraction pattern provided in FIG. 3 , and wherein the composition contains between about 5 mg and about 200 mg of 5-azacytidine.