Abstract
Effect of dicarboxylic acids : malonic acid (MA), succinic acid (SUA), and glutaric acid (GA), on the preferential cocrystal formation with carbamazepine (CBZ) was investigated. Stoichiometries of CBZ / MA, CBZ / SUA and CBZ / GA cocrystals formed were 2 / 1, 2 / 1 and 1 / 1. When CBZ / SUA ground mixture (GM) was coground with MA, CBZ / SUA cocrystal still remained, i.e., no exchange reaction occurred. On the other hand, exchange reaction occurred when CBZ / MA GM was coground with SUA. CBZ / SUA cocrystal was formed by ternary cogrinding of CBZ, MA and SUA. In CBZ, MA and GA system, preferential cocrystal formation was observed for CBZ / GA. The results of cryogenic cogrinding suggested that preferential CBZ / GA cocrystal formation was due to the stable and rapid crystallization. Preferential CBZ /GA cocrystal formation was assumed when CBZ, SUA and GA ternary cogrinding was performed. Structure and stability of cocrystal, mechanism of cocrystal formation and grinding energy affected the preferential cocrystal former exchange reactions.
