Journal of Inclusion Phenomena and Macrocyclic Chemistry
44 (1-4): 159-161, December 2002
Copyright © 2002 Kluwer Academic Publishers
All rights reserved
Prolonged Plasma Levels of Ketoprofen after Oral Administration of Its α-Cyclodextrin Conjugate/Ethylcellulose Dispersion in Rats
Fumitoshi Hirayama, Makoto Kamada, Hideki Yano, Koichi Udo, Hidetoshi Arima, Kaneto Uekama
Author for correspondence Faculty of Pharmaceutical Sciences, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan
Abstract
6A-O-[2-(3-benzoylphenyl)propinoyl]-α-cyclodextrin (KP/α-CyD conjugate), in which an anti-inflammatory drug, ketoprofen (KP), is covalently bound to one of the primary hydroxyl groups of α-cyclodextrin, was prepared, and the CyD conjugate-based prolonged-release system was designed by combining the KP/α-CyD conjugate (used as a delayed-release fraction) with the KP/ethylcellulose (EC) solid dispersion (used as a slow-release fraction). The conjugate showed a typical delayed-release pattern after oral administration to rats, i.e., plasma levels of KP increased after a lag time of about 3 h and reached a maximum concentration at about 9 h. The co-administration of the conjugate and the EC solid dispersion gave a sustained-release pattern of KP, i.e., a constant plasma KP level was maintained for at least 24 h. The long circulating release patterns in plasma KP levels after oral administration were reflected in the anti-inflammatory effect using with carrageenan-induced acute edema in rat paw.

Keywords
anti-inflammatory effect, colon-specific delivery, cyclodextrin conjugate, delayed-release, ketoprofen, sustained-release