Abstract:

As a widely used generic dosage form with complex development, transdermal patches pose high challenges in conducting clinical bioequivalence studies. In response, regulatory authorities encourage the adoption of physiologically based pharmacokinetic (PBPK) model-guided development to reduce costs and improve success rates. The key influencing factors for PBPK modeling of transdermal patches include drug properties, formulation systems, and inter-individual variations. Regarding drug factors, quantitative structure-property relationship (QSPR) models predict partition and diffusion coefficients based on parameters like molecular weight and lipophilicity (LogP). Mechanistic models elucidate permeation kinetics by resolving the multilayered skin structure. For formulation systems, release differences between matrix-type and reservoir-type patches can be simulated using the multiphase multilayered mechanistic dermal absorption (MPML MechDermA) model, covering key processes like dissolution, precipitation, and vehicle evaporation. Concerning inter-individual variability, factors like skin thickness, pH, appendage density, and pathological states significantly impact permeation efficiency. Models require calibration using variables such as age, gender, and race. The model integrates drug transport equations between compartments based on Fick's law, supporting in vitro-in vivo extrapolation (IVIVE). This article systematically reviews the PBPK modeling methods and their influencing factors in the development of transdermal patches, promising to reduce animal experiments and accelerate clinical translation.

Key words: transdermal patches, physiologically based pharmacokinetic, drug factors, formulation factors, physiological factors