Pharmaceutical compositions comprising forms of 5-azacytidine
The invention provides novel polymorphic and pseudopolymorphic crystalline forms of 5-azacytidine, along with methods for preparing said forms, wherein 5-azacytidine is represented by the formula: The invention also includes pharmaceutical compositions comprising said forms.
1. A pharmaceutical composition for oral administration comprising Form I and Form VII of 5-azacytidine substantially free of other forms of 5-azacytidine.
2. The pharmaceutical composition of claim 1 , wherein the Form VII of 5-azacytidine is characterized by X-Ray Powder Diffraction peaks at approximately 5.8, 11.5, 12.8, 22.4, and 26.6 degrees 2θ.
3. The pharmaceutical composition of claim 1 , wherein the Form I and Form VII of 5-azacytidine is characterized by X-Ray Powder Diffraction peaks at the following 2θ angles:
2θ Angle (degree)
5.779
11.537
12.208
12.759
13.048
14.418
16.489
18.649
19.101
20.200
20.769
21.355
22.365
23.049
23.884
26.628
27.145
29.296
29.582
32.078.
4. The pharmaceutical composition of claim 1 , wherein the Form I and Form VII of 5-azacytidine is characterized by an X-ray powder diffraction pattern corresponding to the representative X-Ray Powder Diffraction Pattern provided in FIG. 7 .
5. The pharmaceutical composition of claim 1 , wherein the Form I and Form VII of 5-azacytidine has a thermogravimetric analysis thermogram comprising a weight loss of about 2.45% between ambient temperature and 150° C.
6. The pharmaceutical composition of claim 1 , wherein the Form I and Form VII of 5-azacytidine has a differential scanning calorimetry thermogram comprising an endotherm with a peak temperature of about 68.3° C.
7. The pharmaceutical composition of claim 1 , which is in a single unit dosage form.
8. The pharmaceutical composition of claim 1 , which is a tablet.
9. The pharmaceutical composition of claim 1 , which is a capsule.
10. The pharmaceutical composition of claim 1 , which contains between about 5 mg and about 200 mg of 5-azacytidine.
11. The pharmaceutical composition of claim 10 , which contains about 100 mg of 5-azacytidine.
12. The pharmaceutical composition of claim 1 , which further comprises a carrier, diluent, or excipient.
13. The pharmaceutical composition of claim 12 , which comprises at least one of mannitol, microcrystalline cellulose, and magnesium stearate.