Understanding Formulation and Temperature Effects on Dermal Transport Kinetics by IVPT and Multiphysics Simulation

Pharm Res. 2022 May;39(5):893-905. doi: 10.1007/s11095-022-03283-1. Epub 2022 May 16.

Abstract

Purpose: It is often unclear how complex topical product formulation factors influence the transport kinetics through skin tissue layers, because of multiple confounding attributes. Environmental factors such as temperature effect are also poorly understood. In vitro permeation testing (IVPT) is frequently used to evaluate drug absorption across skin, but the flux results from these studies are from a combination of mechanistic processes.

Method: Two different commercially available formulations of oxybenzone-containing sunscreen cream and continuous spray were evaluated by IVPT in human skin. Temperature influence between typical skin surface temperature (32°C) and an elevated 37°C was also assessed. Furthermore, a multiphysics-based simulation model was developed and utilized to compute the flux of modeled formulations.

Results: Drug transport kinetics differed significantly between the two drug products. Flux was greatly influenced by the environmental temperature. The multiphysical simulation results could reproduce the experimental observations. The computation further indicated that the drug diffusion coefficient plays a dominant role in drug transport kinetics, influenced by the water content which is also affected by temperature.

Conclusion: The in vitro testing and bottom-up simulation shed insight into the mechanism of dermal absorption kinetics from dissimilar topical products.

Keywords: computational fluid dynamics; diffusion; flux; in vitro permeation test; topical delivery.

MeSH terms

  • Administration, Cutaneous
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Permeability
  • Skin Absorption*
  • Skin* / metabolism
  • Temperature