A correlation of flux through a silicone membrane with flux through hairless mouse skin and human skin in vitro

The maximum fluxes of 32 prodrugs and parabens through polydimethylsiloxane membranes from water (EXP log JMPAQ) have been correlated with the maximum flux of the same prodrugs and parabens through hairless mouse skin from water (EXP log JMMAQ): EXP log JMMAQ = 0.608 EXP log JMPAQ − 0.636, r2 = 0.743. The average of the absolute values for the differences between the EXP log JMMAQ and the log JMMAQ calculated from EXP log JMPAQ (Δ log JMMAQ) was 0.227 log units. Similarly the maximum fluxes of 11 unrelated permeants through human skin from water (EXP log JMHAQ) was correlated with the EXP log JMPAQ for the same permeants: EXP log JMHAQ = 0.516 EXP log JMPAQ − 0.922, r2 = 0.82 and Δ log JMHAQ = 0.252 log units. Since the best fit of the databases for EXP log JMPAQ, log JMMAQ and log JMHAQ was to the Roberts–Sloan (RS) model, and the dependency of RS on a balance in lipid and aqueous solubility for optimization of topical delivery has been established, the present correlation suggests that the flux through a silicone can be used to predict flux through mouse or human and that the physicochemical properties that lead to optimized flux through one membrane will lead to optimized flux through the others.