Cocrystals of carbamazepine: Structure, mechanical properties, fluorescence properties, solubility, and dissolution rate

Abstract

Carbamazepine (CBZ) is an anticonvulsant with very low water solubility, presenting as a white crystalline powder with poor mechanical properties and is hard to bend. To enhance CBZ’s physicochemical properties, such as water solubility and mechanical properties, we selected six cocrystal coformers (CCFs): nicotinamide (NIC), benzamide (BZM), salicylic acid (SCA), fumaric acid (FMA), trimesic acid (TMA), and hesperetin (HPE). Six CBZ cocrystals were successfully prepared using the solution method. Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and single crystal X-ray diffraction (SCXRD) were used to characterize the crystal structures and gain comprehensive insights into the six cocrystals. The mechanical, fluorescence, and solubility properties of the six cocrystals were tested. The results reveal that most of the prepared cocrystals exhibit improved water solubility and mechanical properties when compared to CBZ. Among them, the dissolution rate of cocrystals excluded from CBZ-HPE has increased by an average of 3 or 4 times compared to CBZ, while CBZ-HPE exhibits superior mechanical properties. Moreover, all six cocrystals possess better fluorescence performance than CBZ. We thoroughly evaluated the mechanical properties of the cocrystals through both experimental and theoretical approaches. This work provides a new direction for studying drug cocrystals to improve the physicochemical properties of drugs.