Multicomponent Crystal Forms of Albendazole for Bioavailability Improvement

Abstract

In this study, a large-scale screening of multicomponent crystal forms of albendazole (ABZ) was carried out, aiming to improve its solubility and dissolution rate for bioavailability improvement. A computational prescreening tool based on the hydrogen bond energy was employed for initial selection of the coformer candidates to shorten the period and number of the experimental investigations, leading to the discovery of eight ABZ multicomponent solids, e.g., 1:1 albendazole-alpha-ketoglutaric acid (ABZ-AKA), 1:1 albendazole - etidronic acid (ABZ-ETA), 1:1 albendazole - (R)-mandelic acid (ABZ-RMA), albendazole - (S)-mandelic acid (1:1 ABZ-SMA), albendazole - citraconic acid (1:1 ABZ-CTA), 1:1 albendazole - mandelic acid (ABZ-MDA), 1:1 albendazole - cyclamic acid (ABZ-CYA), and albendazole - malonic acid (1:1 ABZ-MLA). Although these solids are salt cocrystal adducts based on the ΔpK_a rule, they are all salt forms according to the structure analyses and FTIR results. The dissolution study has shown that the cocrystals of both ABZ-ETA and ABZ-CYA significantly improved the ABZ dissolution performance in comparison with the parent drug of ABZ.