Do partition coefficients (liphophilicity/hydrophilicity) predict effects of occlusion on percutaneous penetration in vitro: a retrospective review

Abstract

Context: Skin occlusion influences percutaneous penetration by limiting penetrant evaporation, but also through impeding loss of water from skin and increasing the hydration state of the stratum corneum, thus dramatically altering the physiological nature of the stratum corneum. In general, occlusion is widely utilized to enhance penetration of applied drugs in clinical practice; however, occlusion does not increase the percutaneous absorption of all chemicals.

Objective: We focus on what effect occlusion has on the in vitro percutaneous absorption of compounds of varying lipophilicities/hydrophilicities.

Methods: Studies and prior reviews of the effects of occlusion on the in vitro percutaneous penetration of penetrants of varying lipophilicities/hydrophilicities were identified in the MEDLINE, PubMED, Embase and Science Citation Index databases using the terms occlusive, occluded, occlusion, in vitro, skin and percutaneous absorption/penetration to generate as broad of a search as possible. From the results generated, abstracts were subsequently scrutinized to identify articles dealing primarily with in vitro models of the skin involving occlusion. Moreover, after the identification of relevant articles, their references were examined to find additional sources of information.

Results: After examining the research articles generated by the search results, five original research articles were obtained that used in vitro occlusion models and provided insight regarding the role of partition coefficients in predicting occlusion’s effects on percutaneous penetration; articles that dealt with occlusion and percutaneous penetration but did not shed light on how the lipophilicity/hydrophilicity of a compound could affect occlusion efficacy were excluded. Some of the studies bolster the notion that occlusion-enhanced hydration of the stratum corneum increases the percutaneous absorption of lipophilic molecules more than hydrophilic molecules, which seems to confirm some in vivo studies. However, this effect was not consistent; many studies reviewed did not find that the penetrant’s liphophilicity/hydrophilicity reliably predicted occlusion’s effect on penetration. In these studies, lipophilic compounds did not demonstrate increased percutaneous absorption under occlusion.

Conclusion: Thus, it does not seem that partition coefficients can reliably predict the effect of occlusion on percutaneous penetration in vitro. This suggests skin occlusion may be more complex than previously thought.

• Barrier function
• hydrophilicity
• in vitro
• liphophilicity
• occlusion
• octanol-water partition coefficient
• percutaneous absorption/penetration
• stratum corneum