Crystal structures for the commercial monohydrate form and an anhydrate form of dasatinib, an oral anticancer agent, are presented along with characterization by Raman spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Solubility measurements conducted in water reveal that the anhydrate has dramatically improved solubility compared to the commercial hydrate form. Finally, dasatinib is a rare example of a promiscuous solvate former, and the basis for this behavior can now be understood by examining the poor packing efficiency in the unsolvated form
Initial characterization of DAS phases was carried out with Raman spectroscopy. Both the commercial hydrate and anhydrate phases have several characteristic peaks in 1400− 1700 cm−1 region (Figure 2)
2. Powder X-ray Diffraction.
Microcrystalline samples of hydrate and anhydrate DAS phases were characterized by PXRD to ensure phase identity (Figure 3)
3. Structural Aspects.
DAS molecules have a very high degree of torsional freedom. An overlay of the two symmetry independent molecules from the crystal structures shows that they possess markedly different conformations (Figure 4)
In the present study, two modifications of DAS, a hydrate and an anhydrate, were characterized and their physiochemical relationships were established. Moreover, crystal structures of both modifications were determined. DAS readily incorporates water or organic solvents in its crystal lattice during processing or crystallization, and this promiscuous solvation behavior is driven by close packing considerations. Bulk access to a pure and stable anhydrate modification of this compound was achieved through mixed solvent systems. DAS anhydrate obtained in our present study is stable and has major solubility advantages that may motivate using this form over the commercial hydrate modification in future formulations of this important oral anticancer agent