Insight into polymorphism and dynamics of aripiprazole
Abstract
Phase sequence and molecular dynamics (molecular relaxation processes) of aripiprazole were studied by X-ray diffraction (XRD), differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and broadband dielectric spectroscopy (BDS). Polymorphism of aripiprazole depends strongly on thermal treatment. A double glass transition was observed for a sample cooled rapidly from a liquid state. During slow cooling, aripiprazole forms a mixture of a solid phase and glass of a liquid phase. Different polymorphism is observed during slow (2 K min−1) and fast (5–20 K min−1) temperature changes. New crystal phases, which have not been identified yet, were observed during a slow process of cooling/heating. Form III and form IV crystallize simultaneously during heating after fast cooling. XRD experiments and segmentation of POM textures allow us to estimate the contribution of each form as a function of temperature. Complex molecular mobility was found both in crystalline phases and during the softening of the glass.