Stratum corneum reservoir as a predictive method for in vitro percutaneous absorption

Area of Science:

• Pharmacokinetics
• Dermal Absorption
• Drug Delivery

Background:

• Drug interaction with stratum corneum (SC) lipids and proteins is crucial for absorption.
• Previous in vivo studies suggested SC drug levels at 30 minutes predict 96-hour penetration.
• Validating this in vitro could advance transdermal drug delivery platform testing.

Purpose of the Study:

• To determine the in vitro penetration behavior of compounds across human SC.
• To establish the relationship between SC reservoir quantity at 30 minutes and 24-hour skin absorption/penetration.

Main Methods:

• Utilized in vitro models with human skin.
• Quantified the amount of compound in the SC reservoir at 30 minutes post-application.
• Correlated SC reservoir levels with 24-hour skin absorption and penetration data.

Main Results:

• The study reaffirmed the SC reservoir effect for predicting topical compound absorption and penetration.
• Statistically significant linear relationships were found between the 30-minute SC quantity and 24-hour absorption/penetration.
• The SC acts as a rate-limiting barrier, with subsequent deeper penetration occurring rapidly.

Conclusions:

• The quantity of a compound in the SC reservoir at 30 minutes can serve as a reliable proxy for longer-term (24-hour) skin absorption and penetration.
• This finding simplifies assays for quantifying topical compound penetration capacity.
• Further research with diverse compounds is recommended to fully elucidate these observations.