Benexate.CD, a new orally active antiulcer agent, is an inclusion compound of
benexate and
beta-cyclodextrin (beta-CD). The present report investigated the significance of complex formation on the antiulcer activity of
benexate, the effective ingredient of
benexate.CD. To evaluate the improvement of solubility, the dissolution properties of
benexate from various
pharmaceutical forms into the 1st fluid of the Pharmacopoeia of Japan, a model of gastric juice, were compared.
Benexate itself was hardly soluble, but the physical mixture of
benexate and beta-CD showed a solubility increase of
benexate. On the other hand,
benexate.CD showed a supersaturated dissolution curve and its peak concentration was 8 times higher than the solubility of the physical mixture. When
benexate.CD was administered orally to pylorus ligated rats in the
powder formulation, the similar supersaturated dissolution behavior was observed in the stomach, and the
benexate level in gastric tissue was higher than that in
benexate or the physical mixture administration.
Benexate.CD extremely inhibited the
ulcer formation caused by HCl-
ethanol ingestion, but there was no significant inhibition
after treatment with
benexate or the physical mixture. These results indicated that it is necessary for
benexate to form an inclusion compound in order to exert a strong antiulcer activity.