Improvement of the Bioavailability and Anti-hepatic Alveolar Echinococcosis Effect of Albendazole-Isethionate/Hypromellose Acetate Succinate (HPMC-AS) Complex

Abstract

Maximizing the pharmacodynamics of albendazole (ABZ), which is used to treat echinococcoses, is essential for the long-term treatment of echinococcosis patients. ABZ is a weak base whose solubility depends on the pH value of the solvent. ABSTRACT Maximizing the pharmacodynamics of albendazole (ABZ), which is used to treat echinococcoses, is essential for the long-term treatment of echinococcosis patients. ABZ is a weak base whose solubility depends on the pH value of the solvent. After it has been orally administered, its solubility drops sharply from when it is in gastric juices (pH 1.4) to when it is in intestinal juices (pH 6.5) and is subsequently absorbed in the ileum and jejunum. This results in low solubility and poor bioavailability of the drug. In this study, we developed an orally administered albendazole-isethionate (ABZ-HES)/hypromellose acetate succinate (HPMC-AS) complex tablet (TABZ-HES-H) with improved solubility and bioavailability. Previous studies demonstrated that ABZ-HES has a higher intrinsic dissolution rate under pH 1.4 than the ABZ free base used in the commercial product Albenda and that HPMC-AS can effectively inhibit ABZ crystallization, which could be due to the hydrophobic interaction between ABZ and HPMC-AS in an aqueous environment. In this study, the dissolution behavior of TABZ-HES-H in vitro was studied by the two-step pH conversion method. Our results demonstrated that the oral bioavailability of TABZ-HES-H was approximately 2.6 times higher than that of ABZ. More importantly, in the rat model of secondary hepatic alveolar echinococcosis, the anti-hepatic alveolar echinococcosis effect of TABZ-HES-H was 3.4 times higher than that of a commercial product. The improved preparation with salt and polymer has proven to be a feasible method of improving the oral bioavailability and pharmacodynamics of ABZ.