In-vitro percutaneous studies with 5% acyclovir cream: Histopathological evidence for time dependant diffusivity

Percutaneous drug penetration studies were performed, during which skin properties were altered. The present research characterizes, in particular, the in vitro permeation kinetics of a 5% acyclovir cream through hairless mouse skin. Cumulative amounts of penetrated acyclovir per 1 cm² area were monitored in a Franz diffusion cell system. Statistical models were constructed to interpolate the experimental data obtained from 11 sets of experiments (each, n = 6). Thein vitro penetration of acyclovir through hairless mouse skin over a 24-h period was found to be non-linear, with a slow "early phase" up to 12 hours, followed by a rapid "late phase" (approximately 10 times faster). The histological finding of epidermal necrosis in the latter period - but not in the first 12 hours - probably explains the non-linear elevation of the drug transport rate in the diffusion study. The data presented in this paper demonstrate a phenomenon, involving slow deterioration of skin tissue, which complicates the prediction of the diffusive behavior of drug-vehicle compositions penetrating through excised skinin-vitro.