A two-layer diffusive model for describing the variability of transdermal drug permeation

Area of Science:

• Pharmacokinetics and Drug Delivery
• Computational Modeling
• Physical Chemistry

Background:

• Transdermal drug permeation is crucial for drug delivery.
• Permeability coefficients (k(p)) are key metrics, but their distribution is often non-symmetrical.
• Existing models do not fully explain the observed variability in k(p) distributions.

Purpose of the Study:

• To develop a theoretical model explaining the non-symmetrical distribution of permeability coefficients (k(p)) in transdermal drug permeation.
• To investigate the relationship between drug permeation rate and the symmetry of k(p) distributions.
• To provide a framework for analyzing flux variabilities in transdermal drug delivery.

Main Methods:

• Development of a two-layer model for transdermal drug permeation.
• Application of the model to explain k(p) variability data for five different drugs from published studies.
• Analysis of how drug permeation speed influences the skewness of k(p) distributions.

Main Results:

• The two-layer model successfully explains the observed k(p) variabilities for the studied drugs.
• Rapidly permeating drugs exhibit more symmetrical k(p) distributions.
• Slowly permeating drugs show progressively more positively skewed k(p) distributions.

Conclusions:

• The proposed two-layer model provides a theoretical basis for understanding non-symmetrical k(p) distributions in transdermal drug permeation.
• Drug permeation rate is a critical factor influencing the statistical distribution of permeability coefficients.
• Future research on transdermal flux variability should consider the impact of drug properties on k(p) distribution symmetry.