Analysis of 50 Crystal Structures Containing Carbamazepine Using the Materials Module of Mercury CSD

A set of 50 crystal structures containing the molecule carbamazepine (CBZ) have been analyzed using the Materials module within Mercury CSD 2.0. The similarity relationships between all 50 structures were determined based on the analysis of packing motifs. Packing motifs that define the similarity relationships within three separate groups of structures were found to be exclusive to a particular group. The carboxamide homodimer found in all four of the carbamazepine polymorphs is seen to be disfavored compared to the carboxamide-carboxylic acid heterodimer when a coformer molecule with a carboxylic acid group is present. Etter's rules are found to be broken in a large percentage of the CBZ structures (24%) compared to the overall CSD statistics (2.5%), apparently due to steric hindrance caused by the dibenzazepine group. A group of 14 similar structures has been identified containing ordered or disordered coformer-filled channels. Thirteen new crystal structures containing CBZ and pharmaceutically relevant carboxylic acid coformers are reported. Pharmaceutically relevant concepts are explored including crystal packing relationships, motif stability, hydrogen-bond competition, isostructurality, void visualization, and rational crystal design.