Occlusion Effect on in vivo Percutaneous Penetration of Chemicals in Man and Monkey: Partition Coefficient Effects

Abstract

Background/Aim: Skin occlusion can increase the hydration of the stratum corneum up to 50%, which can have substantial effects on the percutaneous absorption of penetrants by altering skin barrier physiology. Though occlusion is widely utilized to enhance the penetration of applied drugs in clinical practice, it is not well known for which chemicals occlusion enhances the penetration through skin. In this review, we focus on what effect occlusion has on the percutaneous absorption of compounds of varying lipophilicities/hydrophilicities in vivo in the monkey and man. Methods: Studies and prior reviews of the effects of occlusion on the in vivo percutaneous penetration of penetrants of varying liphophilicities/hydrophilicities were identified in the Medline, Pubmed, Embase and Science Citation Index databases. Results: After examining the research articles generated by the search results, 7 original research studies were obtained that used in vivo occlusion models and provided insight regarding the role of partition coefficients in predicting the effects of occlusion on percutaneous penetration. From these studies, one can conclude the following: (1) occlusion enhances the percutaneous absorption of many but not all compounds, (2) penetration can increase as the amount of time of occlusion increases, (3) occlusion seems to enhance the penetration of very lipophilic compounds more than that of very hydrophilic compounds, but (4) a relationship between a compound’s octanol-water partition coefficient and its occlusion-induced enhancement has not been determined. Conclusion: These in vivo studies reinforce the conclusions drawn from in vitro studies that partition coefficients incompletely predict the effect of occlusion on percutaneous penetration.

Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin

“…It also seems likely that occlusion by the sebum film (height approx. 20 µm) could have hydrated the skin and potentiated the transdermal flux [52, 53]. We note that there may also be a chemical-specific skin penetration enhancement effect from the oleic acid present at a high level (30%) in the artificial sebum.…”

A framework incorporating the impact of exposure scenarios and application conditions on risk assessment of chemicals applied to skin

“…The largest differences in C p, ss values were obtained from switching between occlusion and non-occlusion and water-diluted (with 90% water) vs. neat application. Occlusion increases skin penetration of many compounds due to increased hydration of the stratum corneum and, in the case of volatile compounds, prevention of evaporation (Hafeez and Maibach 2013 ). The presence of a large volume of water in the 90% dilution affected the C p, ss of the most hydrophilic and water-soluble chemicals (DGMME, DMF and 2-ME) to the greatest extent.…”

Starch-Based Pickering Emulsions as Platforms for Topical Antibiotic Delivery: In Vitro and In Vivo Studies

“…On the other hand, LP is a non-polar solvent, creating an occlusive barrier onto the membrane. It was demonstrated that the occlusion effect is widely used to enhance the penetration of applied drugs in clinical practice [33]. However, occlusion does not increase percutaneous absorption of all chemicals, being more effective for lipid-soluble, non-polar molecules but less efficient for polar molecules, which is the case of MH [34].…”