An econazole β-cyclodextrin inclusion complex: an unusual dissolution rate, supersaturation, and biological efficacy example

Abstract

Genuine cyclodextrin inclusion complexes of the antimycotic econazole and β-cyclodextrin had higher antimycotic activity than a physical mixture of econazole and β-cyclodextrin. Surprisingly, the econazole dissolution rate from the physical mixture was higher than the dissolution rate from the inclusion complex. The improved antimycotic activity of the inclusion complex might be due to the superior ability of the complex to cause econazole supersaturation. A new procedure was applied to disclose the drug supersaturation. The genuine inclusion complex molar ratio econazole: β-cyclodextrin 2:3 gave rise to more hemolysis than the corresponding physical mixture. Toxicity testing on a human buccal epithelium in vitro model — based on TR146 cells — showed that the physical mixture was more toxic than the inclusion complex when TR146 cell mortality was evaluated. Neither measurement of the transepithelial electrical resistance of TR146 cell layers exposed to either the physical mixture or the inclusion complex nor analysis of the protein liberation from the TR146 cells during exposure revealed any differences between the two compositions.