Effect of heat on the percutaneous absorption and skin retention of three model penetrants

The effect of heat on the transdermal delivery of model penetrants of differing lipophilicity through artificial membranes (non-rate limiting) and human epidermis was investigated in vitro. Saturated suspensions of the model penetrants; methyl paraben (MP), butyl paraben (BP) and caffeine (CF) in deionised water (vehicle) were used to attain maximal thermodynamic activity. Franz cell experiments were performed at temperatures ranging from 23 to 45 degreesC using the infinite dose method. Artificial membrane studies showed the penetrant diffusivity (diffusion coefficient) in the vehicle to be totally dependent on temperature and not changes in donor solubility. Epidermal flux and retention of all penetrants was found to be affected by temperature. The amount of penetrant retained in the epidermis was found to be in the order BP > CF > MP whilst the transdermal fluxes increased in the order MP > BP > CF with increasing receptor temperature. Estimated epidermal diffusivity of MP was found to be significantly affected by temperature (P less than or equal to 0.05) compared to BP and CF. Using Arrhenius plots, a lower activation energy was recorded for CF and may suggest a difference in permeation kinetics compared to the other penetrants. (C) 2003 Elsevier B.V. All rights reserved.