Improving Pharmaceutical Properties of Thiabendazole through Cocrystallization with Structurally Similar Polyphenol Ligands

In this study, two novel thiabendazole (TBZ) cocrystals were successfully prepared by the solvent evaporation method through the selection of structurally similar, highly water-soluble resorcinol (RES) and phloroglucinol (PHG) as cocrystal formers (CCFs), together with TBZ, which is inherently water-insoluble. The two TBZ cocrystals were comprehensively characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), thermogravimetric-differential scanning calorimetry (TG-DSC), and Fourier-transform IR spectroscopy (FT-IR). Hirshfeld surface analysis was employed to visually illustrate the types and distributions of intermolecular interactions in the two TBZ cocrystals. The solubility and dissolution of the two TBZ cocrystals were measured, respectively. Both cocrystals exhibited superior aqueous solubility compared with TBZ. Specifically, the thiabendazole-phloroglucinol (TBZ-PHG) cocrystal demonstrates that the increased density of hydroxyl groups in the coformer enhances the hydrogen bonding interactions, leading to the formation of a 2 : 1 (TBZ:PHG) stoichiometric cocrystal. The non-parallel arrangement of TBZ molecules in the cocrystal disrupts the close π-π stacking, thereby enhancing solvent penetration. Consequently, its aqueous solubility is improved to a greater extent.