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.
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