Nitazoxanide Cocrystals in Combination with Succinic, Glutaric, and 2,5-Dihydroxybenzoic Acid

Combination of nitazoxanide (NTZ) with a total of 32 cocrystal formers gave cocrystals with succinic acid (NTZ-SUC, 2:1) and glutaric acid (NTZ-GLU, 1:1). Additionally, 2,5-dihydroxybenzoic acid provided a cocrystal solvate with acetonitrile (NTZ-25DHBA-CH3CN, 1:1:1). All solid phases were characterized by X-ray powder diffraction analysis, IR spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and single-crystal X-ray diffraction analysis. Single-crystal X-ray crystallography revealed that NTZ and the carboxylic acid cocrystal formers were linked in all three cocrystals through the same supramolecular heterodimeric synthon, C(N)NH···HOOC. Despite having different stoichiometries, the crystal structures of NTZ-SUC and NTZ-GLU showed similarities in the supramolecular organization, both containing two-dimensional layers formed by NTZ molecules, which were further interconnected by single (NTZ-SUC) and homodimeric entities (NTZ-GLU) of the cocrystal former. Basic physical stability ...