Novel pharmaceutical salts of albendazole

Abstract

Albendazole (ABZ) is a class II safe and effective antihelmintic drug in the benzimidazole group according to the BCS (Biopharmaceutics Classification System) with low solubility (9 mg L-1) and high permeability (logP 2.54). Novel salts and salt hydrates of ABZ are reported with benzene and p-toluene sulfonic acid (BSA, PTSA), as well as carboxylic acids such as oxalic acid (OA), maleic acid (MLE), l-tartaric acid (LTA), 2,6-dihydroxybenzoic acid (2,6-DHBA), and 2,4,6-trihydroxybenzoic acid (2,4,6-THBA). The products ABZ-BSA, ABZ-BSA-H, ABZ-PTSA, ABZ-PTSA-H, ABZ-OA-H and ABZ-2,6-DHBA were confirmed by single crystal X-ray diffraction. In the hydrate structures (designated as -H), the water molecule acts as a bridge in the hydrogen bonding network. The salt formation of ABZ-MLE, ABZ-LTA, and ABZ-2,4,6-THBA was confirmed by 15N ss-NMR based on the chemical shift change of ca. 50 ppm. The sulfonate salt hydrates exhibit 2D isostructurality, and position disorder in the thiopropyl group in the drug crystal structure was not observed in the salts. Crystal lattice energies were calculated for the MLE, LTA, and 2,4,6-THBA complexes of ABZ to confirm the molecular salt formation. The cocrystals of ABZ with the hydroxybenzene carboxylic acids are novel salts in the benzimidazole drugs class.