Modeling Temperature-Dependent Dermal Absorption and Clearance for Transdermal and Topical Drug Applications

AbstractA computational model was developed to better understand the impact of elevated skin temperatures on transdermal drug delivery and dermal clearance. A simultaneous heat and mass transport model with emphasis on transdermal delivery system (TDS) applications was developed to address transient and steady-state temperature effects on dermal absorption. The model was tested using representative data from nicotine TDS applied to human skin eitherin vitro orin vivo. The approximately 2-fold increase of nicotine absorption with a 10 °C increase in skin surface temperature was consistent with a 50–65 kJ/mol activation energy for diffusion in the stratum corneum, with this layer serving as the primary barrier for nicotine absorption. Incorporation of a dermal clearance component into the model revealed efficient removal of ni cotine via the dermal capillaries at both normal and elevated temperatures. Two-compartment pharmacokinetic simulations yielded systemic drug concentrations consistent with the human pharmacokinetic data. Bothin vitro skin permeation andin vivo pharmacokinetics of nicotine delivered from a marketed TDS under normal and elevated temperatures can be satisfactorily described by a simultaneous heat and mass transfer computational model incorporating realistic skin barrier properties and dermal clearance components.
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research