Barrier model selection alters apparent diclofenac permeation parameters: a controlled in vitro comparison of Strat-M® and a HaCaT-based epidermal construct

Abstract

Introduction Synthetic membranes and keratinocyte-based constructs are both used as accessible alternatives to ex vivo skin in in vitro permeation testing (IVPT), but they have not been compared directly for the same marketed products under identical conditions. This pilot study directly compared the synthetic Strat-M® membrane and a HaCaT construct under identical IVPT conditions using Voltaren® and Olfen®, two marketed, nominally dose-equivalent diclofenac gels. The aim was to determine whether the two barrier models yielded consistent apparent permeation parameters and led to the same comparative interpretation of the two formulations. Methods Permeation studies were performed using Franz diffusion cells in an internally controlled experimental design. Both formulations were tested in triplicate under identical conditions, including receptor medium, temperature, sampling protocol, and analytical method. Steady-state flux (Jss), permeability coefficient (Kp), lag time ( t lag), and cumulative permeation profiles were determined and compared between barrier models. Results Barrier model selection affected the apparent permeation behavior of diclofenac. Strat-M® detected a statistically significant difference in steady-state flux between Voltaren® and Olfen®, whereas no statistically significant between-formulation difference was detected with the HaCaT construct under the same experimental conditions. Lag time was the parameter most strongly influenced by barrier selection and was consistently shorter with the HaCaT construct than with Strat-M®. Discussion Under identical IVPT conditions, Strat-M® and the HaCaT-based epidermal construct generated different apparent permeation profiles and yielded different comparative assessments of Voltaren® and Olfen®. This model-dependent divergence underscores the need to justify barrier selection explicitly and to consider its limitations when interpreting comparative IVPT data.