COMBINATION EFFECTS OF O-CARBOXYMETHYL-O-ETHYL-BETA-CYCLODEXTRIN AND PENETRATION ENHANCER HPE-101 ON TRANSDERMAL DELIVERY OF PROSTAGLANDIN-E(1) IN HAIRLESS MICE

An inclusion complex of prostaglandin E1 (PGE1) with beta-cyclodextrin (beta-CyD) or O-carboxymethyl-O-ethyl-beta-cyclodextrin (CME-beta-CyD) was made as topical preparations in a fatty alcohol/propylene glycol ointment base. When the PGE1 preparations were applied onto the skin of hairless mice, the vasodilating effect of the PGE1-CME-beta-CyD complex supplemented with a penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentane-2-one (HPE-101) was approximately 100 times that of the PGE1 alone and approximately 10 times that of PGE1 with HPE-101 or the PGE1-beta-CyD complex with HPE-101. The combination of CME-beta-CyD and HPE-101 enhanced the percutaneous penetration of PGE1 in a synergistic manner; CME-beta-CyD assisted the release of HPE-101 from the ointment base and its entry into the skin, which may facilitate the percutaneous penetration of PGE1. Furthermore, this combination suppressed the bioconversion of PGE1 to give less pharmacologically active metabolites during the passage through the skin, a situation delivering intact PGE1 more effectively to the site of action. The present data suggest that the combination of CME-beta-CyD and HPE-101 is particularly useful for improving topical bioavailability of PGE1.