Forms of 5-Azacytidine
The disclosure includes 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 disclosure also includes pharmaceutical compositions comprising said forms.
1. A method for preparing Form IV of 5-azacytidine substantially free of other forms, the method comprising
crystallizing 5-azacytidine from a solvent mixture comprising dimethylsulfoxide and chloroform by cooling said solution from a temperature selected to allow said 5-azacytidine to dissolve completely to about −20° C.; and
isolating said crystals.
2. A method for preparing Form IV of 5-azacytidine substantially free of other forms, the method comprising:
crystallizing 5-azacytidine from a solvent mixture comprising dimethylsulfoxide and toluene by cooling said solution from a temperature selected to allow said 5-azacytidine to dissolve completely to about ambient temperature; and
isolating said crystals.
3. A method for preparing Form V of 5-azacytidine substantially free of other forms, the method comprising:
crystallizing 5-azacytidine from a solvent mixture comprising dimethylsulfoxide and toluene by cooling said solution from a temperature selected to allow said 5-azacytidine to dissolve completely to about −20° C.; and
isolating said crystals.
4. A method for preparing a mixed phase of Form I of 5-azacytidine and Form VII of 5-azacytidine substantially free of other forms, the method comprising:
crystallizing 5-azacytidine from a solvent mixture comprising dimethylsulfoxide and methanol by cooling said solution from a temperature selected to allow said 5-azacytidine to dissolve completely to about −20° C.; and
isolating said crystals.
5. A method for preparing Form VIII of 5-azacytidine substantially free of other forms, comprising crystallizing 5-azacytidine from N-methyl-2-pyrrolidone and isolating said crystals.