Investigating Cocrystallization of Carbamazepine with Structurally Compatible Coformers: New Cocrystal and Eutectic Phases with Enhanced Dissolution

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, X<inf>CBZ</inf> 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 X<inf>CBZ</inf> 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 X<inf>CBZ</inf> 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-X<inf>CBZ</inf>-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.