Crystallizing Ionic Cocrystals: Structural Characteristics, Thermal Behavior, and Crystallization Development of a Piracetam-CaCl2 Cocrystallization Process

In this study, we aim to develop a robust crystallization process for the ionic cocrystal between piracetam and CaCl2. We discuss the structural characteristics of the piracetam-CaCl2 cocrystal and its thermal behavior; furthermore, we develop a robust crystallization process by construction of appropriate phase diagrams. CaCl2 and piracetam form an ionic dihydrate cocrystal with formula piracetam2·CaCl2·2H2O, in which the Ca2+ cation adopts an octahedral coordination with the oxygens of four different molecules of piracetam and of two water molecules. According to the TGA, DSC, and VT-XRPD, the cocrystal exhibits improved thermal stability compared to the parent drug compound. In this article we show how one can develop a robust, water-based cocrystallization process for ionic cocrystals, a relatively underexplored part of the cocrystal landscape. We also discuss the common ion effect on cocrystallization, and show how a common ion can strongly impact on the solubility of the cocrystal, as well as its co...