Vehicle influence on permeation through intact and compromised skin

Area of Science:

• Dermatology
• Pharmaceutics
• Drug Delivery Systems

Background:

• Transdermal drug delivery offers a non-invasive route for systemic medication.
• Optimizing vehicle composition is crucial for effective drug permeation, especially across compromised skin barriers.
• Understanding how different skin barrier disruptions affect drug penetration is key for formulation development.

Purpose of the Study:

• To compare the transdermal permeation of diclofenac diethylamine from hydrophilic and lipophilic vehicles.
• To evaluate permeation across in vitro models of compromised skin (tape stripping, delipidization, microneedles) versus intact skin.
• To determine the influence of vehicle type on drug delivery through skin with varying degrees of barrier impairment.

Main Methods:

• Utilized in vitro skin models (intact, tape-stripped, delipidized, microneedled) to simulate compromised skin barriers.
• Employed mineral oil as a lipophilic vehicle and 10mM phosphate buffered saline as a hydrophilic vehicle for a model drug (diclofenac diethylamine).
• Measured transepidermal water loss (TEWL) to quantify skin barrier function and correlated it with drug permeation.

Main Results:

• Tape stripping and delipidization significantly increased diclofenac diethylamine permeation compared to intact and microneedle-treated skin for both vehicles.
• Drug permeation across skin followed the order: intact < microneedles < tape stripping < delipidization, correlating with TEWL values.
• In vivo studies with hairless rats confirmed the trend, showing higher delivery with the hydrophilic phosphate buffered saline vehicle.

Conclusions:

• The hydrophilic phosphate buffered saline vehicle demonstrated superior transdermal delivery of diclofenac diethylamine compared to the lipophilic mineral oil vehicle.
• Phosphate buffered saline facilitated greater drug permeation across all tested models of compromised skin.
• Vehicle choice significantly impacts drug delivery efficiency, particularly when skin barrier function is compromised.