Enhanced Bioavailability of Acetohexamide by β-Cyclodextrin Complexation

Abstract

An inclusion complex of the hypoglycemic agent acetohexamide (AHA) with .beta.-cyclodextrin (.beta.-CyD) in the molar ratio of 1:2 was prepared, and its permeation behavior through a cellophane membrane, in situ absorption behavior in rabbit small intestinal tract, and in vivo extent of bioavailability in rabbit were examined in comparison with those of AHA alone. The membrane permeation constant and in situ absorption rate of AHA in solution were found to decrease by the addition of .beta.-CyD. The lesser permeability and absorptivity of the complex were significantly overcome by an improved solubility of AHA. The inclusion complexation of AHA with .beta.-CyD was effective in releasing drug from a hydrophobic suppository base, i.e., Witepsol W35. The complex increased highly the levels of plasma concentration and cumulative urinary excretion of AHA and hydroxyhexamide, 1 of the metabolites of AHA, after oral or rectal administration to rabbits. The increase of bioavailability of AHA by the inclusion complexation suggested the possibility of smaller doses and fewer side effects in sulfonylurea therapy.