Combination effects of O-carboxymethyl-O-ethyl-β-cyclodextrin and penetration enhancer HPE-101 on transdermal delivery of prostaglandin E1 in hairless mice

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