Date of Award

January 2014

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Robert Tigelaar

Subject Area(s)

Pharmacology

Abstract

Context: Occlusion is widely utilized to enhance the percutaneous penetration of applied drugs in clinical practice; however, it is not well understood which (type of) chemicals display enhanced penetration through occluded skin. A better understanding of how occlusion affects penetration will have profound effects on drug development and delivery for a variety of dermatological conditions Moreover, from a public health perspective, there is interest in learning about occlusion's ability to either diminish or augment the pernicious effects of hazardous, cutaneous exposures.

Objective: This study was designed to investigate: (1) whether occlusion enhances the percutaneous penetration of the lipophilic salicylic acid or the hydrophilic formaldehyde when compared to non-occlusion, (2) whether occlusion duration affects the penetration of compounds, and (3) whether occlusive films in clinical practice interact with topically-applied chemicals and possibly hinder penetration.

Materials and Methods: Separately, single doses of [14C]-formaldehyde and [14C]-salicylic acid were applied onto human skin overlying diffusion cells under non-occlusion as well as various occlusive time periods (1hr, 4hrs, 8hrs). The percent dose penetrating into each compartment as well the percent dose adhering to the plastic wrap were determined.

Results: The radioactivity recovery as percent of applied dose of [14C]-salicylic acid was significantly higher under occlusion versus non-occlusion in the epidermis, dermis, and receptor fluid after 24 hours (p < 0.05). For [14C]-formaldehyde, no significant statistical differences were observed between occlusion versus non-occlusion. The plastic wrap often used to enhance the penetration of topically applied drugs does not itself substantially adhere to the tested chemicals.

Conclusion: Occlusion duration, previously undocumented for in vitro studies, impacted the percutaneous penetration of the lipophilic salicylic acid more so than the hydrophilic formaldehyde. A strong correlation between occlusion-enhanced penetration and partition coefficients was observed, but we do not wish to overgeneralize these results until more compounds of varying physical-chemical properties are studied.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

Share

COinS