Pharmaceutical cocrystals of ethenzamide: structural, solubility and dissolution studies

Pharmaceutical cocrystals involving an analgesic drug, ethenzamide (EA) and coformers, such as salicylic acid (SA), 2-chloro-4-nitrobenzoic acid (CNBA), vanillic acid (VA), 4-aminobenzoic acid (ABA), 4-hydroxybenzoic acid (HBA), and fumaric acid (FA) were prepared and characterized by single crystal X-ray diffraction. Physicochemical properties such as solubility and dissolution rate were measured and it was found that all the cocrystals dissolve faster and their equilibrium solubility is higher than the parent EA. Analysis of the crystal structures revealed that of the six cocrystals reported, four of them are sustained by carboxylic acid-carboxamide supramolecular heterosynthon (with coformers SA, CNBA, VA and FA). The crystal structure of EA.ABA features an amide-amide homosynthon and the crystal structure of EA.HBA represents a rare example wherein amide-amide catemer synthon and acid-acid homosynthons coexist. Conformational analysis revealed that the EA molecule adopts a planar conformation in all the cocrystals, in contrast to a twisted conformation in its parent crystal structure.