Improved transdermal delivery of prostaglandin E1 through hairless mouse skin: combined use of carboxymethyl-ethyl-beta-cyclodextrin and penetration enhancers.
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.
Uekama
K
K
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Adachi
H
H
Irie
T
T
Yano
T
T
Saita
M
M
Noda
K
K
D000279:Administration, Cutaneous; D000527:Alprostadil / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001381:Azepines; D003505:Cyclodextrins; D004337:Drug Carriers; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D009824:Ointments; D011758:Pyrroles; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply; D012869:Skin Absorption; D047392:beta-Cyclodextrins
D001381:Azepines; D003505:Cyclodextrins; D004337:Drug Carriers; C062590:O-carboxymethyl-O-ethyl-beta-cyclodextrin; D009824:Ointments; D011758:Pyrroles; D047392:beta-Cyclodextrins; C035229:laurocapram; C075725:1-(2-(decylthio)ethyl)azacyclopentane-2-one; D000527:Alprostadil