Influence of Coformer Stoichiometric Ratio on Pharmaceutical Cocrystal Dissolution: Three Cocrystals of Carbamazepine/4-Aminobenzoic Acid

Cocrystallization
is a technique to optimize solid forms that shows
great potential to improve the solubility of active pharmaceutical
ingredients (APIs). In some systems, an API can form cocrystals in
multiple stoichiometries with the same coformer. However, it remains
unclear how coformer stoichiometry influences solubility. This paper
investigates the pharmaceutical:coformer pair carbamazepine (CBZ)/p-aminobenzoic acid (PABA); both CBZ/PABA 1:1 and 2:1 cocrystals
are known, and a novel 4:1 CBZ/PABA cocrystal is reported here. The
4:1 cocrystal is structurally characterized, and phase stability data
suggest that it is a thermodynamically unstable form. Dissolution
experiments show that there is no correlation between the cocrystal
stoichiometry and dissolution rate in this system. On the other hand,
with the relatively weak intermolecular interactions, metastable forms
can be beneficial to dissolution rate, which suggests that more effort
should be devoted to cocrystal production with kinetic growth methods.