(140c) Mathematical Modeling of Percutaneous Absorption of Volatile Organic Liquids

Skin is the largest organ of the human body and due to its immediate proximity to the environment is often exposed to direct contact with a variety of extraneous chemical and biological substances. A proper study of percutaneous absorption is critical and central to the risk assessment pertaining to variety of exposure scenarios (occupational and environmental) and also for the development, as well as function and safety of transdermal products (cosmetic and therapeutic). The number of chemicals to which the human population is exposed on a daily basis is so high that only a small fraction can be studied experimentally and, thus, computational models for dermal absorption are increasingly used in lieu of animal experiments to estimate absorption of new ingredients and such a predictive approach is widely used in many industries. The exposure scenario for volatile chemicals is further complicated due to the permeant evaporation that influences its tendency to penetrate. Moreover, this evaporation, together with a high heat of vaporization, may decrease the system temperature, thereby influencing the combined evaporation-absorption characteristics of the system. This presentation discusses the development of a mathematical model for predicting skin permeability of volatile compounds using the fundamental principles of transport phenomena and solution thermodynamics. It is also tied to a proper understanding of the intricacies of skin microstructure and their relationship to the actual mechanism of percutaneous penetration. The essential features of the model, the development of model equations and the required initial, boundary (and auxiliary) conditions, the assumptions and approximations incorporated in them, and, finally the solution methodology are discussed in detail. The key features of the model include treatment of the moving boundary (representing finite dose volumes), treatment of multilayered problems, coupled heat and mass transfer relevant to volatile substances and, convection due to density gradients (relevant for binary and multicomponent systems). In order to elucidate the associated thermal effect of changing temperature in such evaporation-absorption systems, an isothermal (mass transfer) model and a non-isothermal (coupled heat and mass transfer) model has been developed. These models are then validated through comparing the respective simulation results with corresponding experimental data on the skin permeation fluxes of pure ethanol. The results show appreciable correlation between the model predictions (both isothermal and non-isothermal) and the experimental data (flux and cumulative flux profile). The results also show that the thermal effect in this case is negligible and the system can be appropriately described through an isothermal mass-transfer model.