Journal of Inclusion Phenomena and Macrocyclic Chemistry
44 (1-4): 93-96, December 2002
Copyright © 2002 Kluwer Academic Publishers
All rights reserved
Model Analysis for Oral Absorption of a Drug/Cyclodextrin Complex Involving Competitive Inclusion Complexes
Naomi Ono, Fumitoshi Hirayama, Hidetoshi Arima, Kaneto Uekama, J. Howard Rytting
Author for correspondence Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047-2504, USA
Abstract
The bioavailability parameters of a drug after oral administration of a preparation containing drug/CyD complexes may be modified by formation of competitive inclusion complexes. In this study, we examined the effects of competitors on drug permeation from its CyD complex through in-vitro artificial membranes and in-situ recirculation conditions, for comparison with the results under in-vivo conditions in the bile duct of cannulated rats. Phenacetin, an antipyretic, was used as a model drug, natural CyDs and maltosyl-β-CyD as host molecules, and benzoic acid derivatives, sodium taurocholate and acetaminophen as competitors. The in-vitro cellophane membrane permeation rate and the in-situ absorption rate of phenacetin were quantitatively predicted by theoretical calculation using the stability constants of drug/CyD and competitor/CyD complexes when CyD weakly interacts with membrane components in lower CyD concentrations (generally below 10 mM). The in-vivo absorption behavior was only qualitatively reproducible by the theoretical calculation, probably because of various physicochemical and physiological factors affecting the absorption. The present results may be useful not only for prediction of intestinal absorption of drugs from CyD preparations, but also for formulation design of CyD preparations containing multi-components.

Keywords
bioavailability, competitive inclusion, competitor, intestinal absorption, permeation rate, phenacetin