# A Four-Layer Numerical Model for Transdermal Drug Delivery: Parameter Optimization and Experimental Validation Using a Franz Diffusion Cell

## TL;DR

This paper introduces a four-layer model for simulating transdermal drug delivery, validated with experiments and showing good agreement with real-world data.

## Contribution

The novel four-layer model captures skin structure and drug diffusion with interfacial partitioning and mass transfer resistance.

## Key findings

- The model showed excellent agreement with experimental data from Franz diffusion cell studies.
- For diclofenac, the SC–RS partition coefficient was close to unity, suggesting a simplified model may suffice for this drug.
- The framework allows for spatial resolution and adaptation to other drugs with interfacial effects.

## Abstract

Background/Objectives: A mechanistic understanding of transdermal drug delivery relies on accurately capturing the layered structure and barrier function of the skin. This study presents a four-layer numerical model that explicitly includes the donor compartment, stratum corneum (SC), viable skin (RS), and receptor compartment. Methods: The model is based on Fickian diffusion and incorporates interfacial partitioning and mass transfer resistance. It is implemented using the finite element method in MATLAB and calibrated through nonlinear least-squares optimization against experimental data from Franz diffusion cell studies using porcine skin. Validation was performed using receptor concentration profiles over time and final drug content in the SC and RS layers, assessed via tape stripping and residual skin analysis. Results: The model provided excellent agreement with experimental data. For diclofenac, the optimized partition coefficient at the SC–RS interface was close to unity, indicating minimal interfacial discontinuity and that a simplified three-layer model may be sufficient for this compound. Conclusions: The proposed four-layer framework provides a physiologically informed and generalizable platform for simulating transdermal drug delivery. It enables spatial resolution, mechanistic interpretation, and flexible adaptation to other drugs and formulations, particularly those with significant interfacial effects or limited lipophilicity.