Sustainable Routes to a Soluble Anthelmintic Thiabendazole Organic Salt

A new organic salt of thiabendazole with p-toluenesulfonic acid was successfully synthesized by mechanochemistry. Notably, the same crystalline form and morphology were obtained both through neat grinding and liquid-assisted grinding using 4-methyltetrahydropyran, a sustainable solvent not yet commonly employed in mechanochemical processes. The resulting salt crystallizes as a hydrate with impressive physical stability for up to 18 months under four storage conditions, including 40 °C. Comprehensive solid-state characterization (PXRD, DSC, TGA, HSM, SEM) confirmed the phase identity, purity, and thermal behavior of the material, while FTIR spectroscopy provided insight into the intermolecular interactions driving salt formation and stabilizing the crystalline water. In comparison to pure thiabendazole, the hydrate salt exhibited a remarkable ~70-fold increase in solubility and significantly improved intrinsic dissolution rate over the entire study period. Importantly, the in vivo evaluation in the Heligmosomoides polygyrus mouse model of the salt and the pure drug revealed similar moderate reductions in worm burden, indicating that salt formation does not compromise anthelmintic efficacy.