betadex and 1-(2-(decylthio)ethyl)azacyclopentane-2-one

The optimal prescription of transdermal preparations of prostaglandin E1 (PGE1) for treatment of peripheral vascular diseases has been investigated. The chemical stability of PGE1 in fatty alcohol/propylene glycol (FAPG) ointment was markedly improved by carboxymethyl-ethyl-beta-cyclodextrin (CME-beta-CyD). Application of a PGE1 ointment containing the penetration enhancer, 1-dodecylazacycloheptane-2-one (Azone) or 1-[2-(decylthio)ethyl]azacyclopentane-2-one (HPE-101), onto the skin of hairless mice showed the increase of blood flow in the skin due to the vasodilating action of PGE1. In particular, the ointment containing a PGE1-CME-beta-CyD complex supplemented with HPE-101 showed the most prominent increase of the blood flow. Compared with other ointments, this ointment was found to show significantly greater transfer of HPE-101 into in-vitro preparations of the skin of hairless mice. Transfer of PGE1 into the skin was thought to be facilitated by this increased transfer of HPE-101. These results suggest that a combination of CME-beta-CyD and HPE-101 is useful for designing PGE1 ointments for topical application with good chemical stability and percutaneous permeability.

Topics: Administration, Cutaneous; Alprostadil; Animals; Azepines; beta-Cyclodextrins; Cyclodextrins; Drug Carriers; Female; Mice; Mice, Hairless; Ointments; Pyrroles; Regional Blood Flow; Skin; Skin Absorption