Multidrug Cocrystal of Anticonvulsants: Influence of Strong Intermolecular Interactions on Physiochemical Properties

A drug-drug cocrystal of two anticonvulsants, lamotrigine and phenobarbital, is presented. In the crystal structure, molecules form heterodimers via N-H···O and N-H···N hydrogen bonding. The intrinsic dissolution rate (IDR) and solubility of the cocrystal were measured in phosphate buffer (pH 7.2) and simulated gastric fluid (without pepsin), and compared to pure APIs. Dissolution experiments found suppressed IDR of the cocrystal with rates in the order pure PB > pure LTG > cocrystal. The solubility measurements were consistent with the dissolution behavior. The presence of strong heterodimers in the cocrystal compared to weaker homodimers in the parent drugs is implicated for the reduced solubility and dissolution rate.