Occlusive and Non-Occlusive Application of Microemulsion for Transdermal Delivery of Progesterone: Mechanistic Studies

摘要

This work evaluated the occlusive versus non-occlusive application of microemulsion (ME) for the transdermal delivery of progesterone. The mechanisms of enhanced skin penetration were investigated. ME comprised of oleic acid, Tween 80, propylene glycol, and water, was used neat or with ethanol as a volatile cosurfactant. The ME formulations enhanced progesterone transdermal flux compared to the saturated drug solution in 14% aqueous propylene glycol (control). Ethanol-containing ME (EME) was better than the ethanol-free system (EFME). Open application of EFME produced a marginal reduction in flux compared to occlusive application. For EME, open application reduced the flux by 26–28% with the flux remaining significantly higher than that obtained with EFME. The mechanistic studies revealed synergism between ethanol and EFME with EME, producing greater flux than the sum of fluxes obtained from 40% ethanol in water and EFME. Penetration enhancement and supersaturation played a role in enhanced transdermal delivery, but other mechanisms were also possible. This study thus introduced EME as a transdermal delivery system for progesterone with good potential for open application as a spray.