Enhanced dissolution and oral bioavailability of α-tocopheryl esters by dimethyl-β-cyclodextrin complexation

Abstract

Inclusion complexation of heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CyD) with α-tocopheryl acetate and α-tocopheryl nicotinate in aqueous solution was studied by the solubility method. The aqueous solubilities of the esters were about 10⁵ times increased by DM-β-CyD complexation. The phase-solubility diagram of the tocopheryl ester-DM-β-CyD systems showed a typicalA _p type, and the stability constants (K) of high-order complexes were estimated by analyzing the upward curvature of the diagrams. The solid complex of α-tocopheryl nicotinate with DM-β-CyD in a molar ratio of 1∶2 was prepared by the kneading method. The dissolution rate of the solid complex was much greater than that of the drug itself, and the rapidly dissolving form of α-tocopheryl nicotinate, as an example, showed a markedly increased bioavailability (about 70-fold) after oral administration to fasted dogs.