The crystal structures of the antimicrobial drug tinidazole [TNZ; systematic name: 1-(2-ethylsulfonylethyl)-2-methyl-5-nitroimidazole, C8H13N3O4S] and the 1:1 cocrystal of TNZ with the naturally occurring compound vanillic acid (VA; systematic name: 4-hydroxy-3-methoxybenzoic acid, C8H8O4), namely, the TNZ-VA cocrystal, were determined by single-crystal X-ray analysis at 100 K. The supramolecular structure of the TNZ-VA cocrystal is composed of a carboxylic acid dimer and an O-H...N(heterocycle) synthon in the form of layers made up of O-H...N and O-H...O hydrogen bonds. The layers are joined via C-H...O hydrogen bonds, π-π stacking and C-H...π interactions. The energy framework analysis, together with interaction energy calculations using the DLPNO-CCSD(T) method, indicates that the TNZ-VA cocrystal inherits strong interactions from the TNZ and VA crystals, which accounts for the enhanced thermal stability and reduced dissolution rate. To the best of our knowledge, this is the first example of a cocrystal containing TNZ.
Keywords: API; antimicrobial; crystal structure; dissolution behaviour; energy framework; pharmaceutical cocrystal; thermal stability; tinidazole; vanillic acid.