Continuous cocrystallisation of carbamazepine and trans-cinnamic acid via melt extrusion processing

Abstract

A solvent free process for the formation of carbamazepine (CBZ)–trans-cinnamic acid (TCA) cocrystals, in stoichiometric ratios, was developed using continuous hot melt extrusion processing. Physicochemical characterization of the CBZ–TCA extrudates included scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and hot stage microscopy to evaluate the shape, morphology, purity and crystallinity of the freshly made cocrystals. The obtained cocrystals were of high quality compared to the prototype produced by a solvent crystallization technique. Furthermore, an in-line NIR probe was used to investigate the gradual formation of cocrystals during extrusion processing. The quality of the CBZ–TCA cocrystals was found to depend on the processing parameters such as temperature and the screw type. The extruded cocrystals showed faster dissolution rates compared to bulk CBZ and the prototype cocrystals.