In Vitro Permeation Test (IVPT) for Pharmacokinetic Assessment of Topical Dermatological Formulations

Abstract In vitro assessment of topical (dermal) pharmacokinetics is a critical aspect of the drug development process for semi‐solid products (e.g., solutions, foams, sprays, creams, gels, lotions, ointments), allowing for informed selection of new chemical entities, optimization of prototype formulations during the nonclinical stage, and determination of bioequivalence of generics. It can also serve as a tool to further understand the impact of different excipients on drug delivery, product quality, and formulation microstructure when used in parallel with other techniques, such as analyses of rheology, viscosity, microscopic characteristics, release rate, particle size, and oil droplet size distribution. The in vitro permeation test (IVPT), also known as in vitro skin penetration/permeation test, typically uses ex vivo human skin in conjunction with diffusion cells, such as Franz (or vertical) or Bronaugh (or flow‐through) diffusion cells, and is the technique of choice for dermal pharmacokinetics assessment. Successful execution of the IVPT also involves the development and use of fit‐for‐purpose bioanalytical methods and procedures. The protocols described herein provide detailed steps for execution of the IVPT utilizing flow‐through diffusion cells and for key aspects of the development of a liquid chromatography–tandem mass spectrometry method intended for analysis of the generated samples (epidermis, dermis, and receptor solution). © 2020 Wiley Periodicals LLC. Basic Protocol 1 : In vitro permeation test Support Protocol : Dermatoming of ex vivo human skin Basic Protocol 2 : Bioanalytical methodology in the context of the in vitro permeation test