Improved transdermal delivery of prostaglandin E1 through hairless mouse skin: combined use of carboxymethyl-ethyl-beta-cyclodextrin and penetration enhancers

J Pharm Pharmacol. 1992 Feb;44(2):119-21. doi: 10.1111/j.2042-7158.1992.tb03574.x.

Abstract

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.

MeSH terms

  • Administration, Cutaneous
  • Alprostadil / administration & dosage*
  • Alprostadil / pharmacokinetics
  • Alprostadil / pharmacology
  • Animals
  • Azepines
  • Cyclodextrins*
  • Drug Carriers
  • Female
  • Mice
  • Mice, Hairless
  • Ointments
  • Pyrroles
  • Regional Blood Flow / drug effects
  • Skin / blood supply
  • Skin Absorption
  • beta-Cyclodextrins*

Substances

  • Azepines
  • Cyclodextrins
  • Drug Carriers
  • O-carboxymethyl-O-ethyl-beta-cyclodextrin
  • Ointments
  • Pyrroles
  • beta-Cyclodextrins
  • laurocapram
  • 1-(2-(decylthio)ethyl)azacyclopentane-2-one
  • Alprostadil