Molecular dynamics of the cryomilled base and hydrochloride ziprasidones by means of dielectric spectroscopy.

Cryomilling was applied to obtain amorphous forms of the base ziprasidone and its hydrochloride salt. Complete amorphization of both samples was confirmed by differential scanning calorimetry and X-ray measurements. As it turned out, cryogrinding is very effective way to obtain these drugs in the amorphous state, especially because melting of both ziprazidones accompanies significant chemical decomposition as revealed by ultra performance liquid chromatography examination. Consequently, the glassy state cannot be reached in conventional way, that is, by supercooling of melt. Broadband dielectric relaxation measurements were performed on both drugs to describe their molecular dynamics above as well as below their glass transition temperatures (T(g)). We found out that ziprasidone base and its hydrochloride salt differ in T(g) in the same way as it was previously reported for tramadol monohydrate and its hydrochloride. Moreover, our dielectric studies revealed that molecular mobility is not the main factor controlling kinetics of crystallization of both ziprasidones above their T(g) . Below the T(g) relaxation related to water as well as secondary relaxation process originating from the intermolecular interaction (Johari-Goldstein) were identified in the loss spectra of both materials. We have demonstrated that except of local mobility, water is the dominant factor moving both ziprasidones toward recrystallization process. Finally, we have also carried out solubility measurements to show that dissolution rate of the amorphous ziprasidones is much higher with respect to the crystalline samples.