Abstract:
In this work, carbamazepine (CBZ), an anticonvulsant drug was cocrystallized with several structurally complement coformers (coformers with amide, acid and hydrazide functional groups) to enhance its dissolution. CBZ formed a cocrystal phase with acetamide (ACE) when mixtures of CBZ and ACE (containing CBZ mole fractions, XCBZ of 0.25, 0.33, 0.5, and 0.67) were subjected to solid-state grinding (SSG), evaporative crystallization (EC), slurry conversion (SC), and slow cooling crystallization (SLC). Upon heating, the CBZ-ACE cocrystal phase formed from CBZ-ACE mixtures containing XCBZ of 0.25, 0.33 and 0.67 underwent solid-state phase transition to CBZ form I and CBZ cocrytsal phase obtained from the CBZ-ACE mixture containing XCBZ of 0.5 converted to CBZ form III. Interestingly, slow cooling cocrystallization experiments resulted in crystallization of a cocrystal as well as the CBZ dihydrate forms. The powder dissolution studies demonstrated that among the different CBZ-ACE-SSG cocrystal phases, CBZ-ACE-SSG-XCBZ-0.33 cocrystal exhibited 7.47 times improved dissolution whereas the CBZ eutectic phase with nicotinic acid hydrazide (NAH) exhibited 4.93 times increased dissolution when compared to raw CBZ.