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 II of 5-azacytidine substantially free of other forms of 5-azacytidine, wherein the pharmaceutical composition is a tablet or a capsule.
2. The pharmaceutical composition of claim 1 , wherein the Form II of 5-azacytidine is characterized by X-Ray Powder Diffraction peaks at approximately 13.5, 17.6, and 22.3 degrees 2θ.
3. The pharmaceutical composition of claim 1 , wherein the Form I and Form II of 5-azacytidine is characterized by X-Ray Powder Diffraction peaks at the following 2θ angles:
2θ Angle (degree)
12.244
13.082
13.458
14.452
16.521
17.648
18.677
19.093
20.231
21.353
22.309
23.070
23.909
26.641
26.813
27.158
29.309
29.609
30.384
32.074.
4. The pharmaceutical composition of claim 1 , wherein the Form I and Form II of 5-azacytidine is characterized by an X-ray powder diffraction pattern corresponding to the representative X-Ray Powder Diffraction Pattern provided in FIG. 2 .
5. The pharmaceutical composition of claim 1 , wherein the Form I and Form II of 5-azacytidine has a thermogravimetric analysis thermogram comprising a weight loss of about 1.16% between ambient temperature and 150° C.
6. The pharmaceutical composition of claim 1 , wherein the Form I and Form II of 5-azacytidine has a differential scanning calorimetry thermogram comprising a thermal event with an onset at about 229.8° 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.