Fenamate Cocrystals with 4,4′-Bipyridine: Structural and Thermodynamic Aspects

Cocrystallization of nonsteroidal anti-inflammatory drug fenamates (N-phenylanthranilic acid (N-PA), niflumic acid0 (NFA), flufenamic acid (FFA), tolfenamic (TFA) and mefenamic acids (MFA)) with 4,4'-bipyridine (BP) has resulted in the formation of cocrystals with a 2:1 molar ratio. Crystal Packing Similarity analysis has revealed that the packing arrangement of the [N-PA+BP], [TFA+BP], and [MFA+BP] cocrystals consists of discrete fragments of the crystal structures of initial APIs connected to each other by BP molecules. In the case of [FFA+BP], the cocrystal contains a previously unseen packing arrangement of FFA molecules which may be a fragment of a new polymorphic FFA form. Differential scanning calorimetry studies show a good correlation between the cocrystal melting temperature and the melting points of the corresponding pure APIs. The enthalpies of cocrystal formation are small, which indicates that the packing energy gain only originates from weak van der Waals interactions between the API and BP molecules.