A comparison of the fit of flux through hairless mouse skin from water data to three model equations

Data for the delivery of total species containing parent drugs from water through hairless mouse skin by prodrugs, log JMMAQ, has been fitted to the Roberts-Sloan, RS, the Kasting-Smith-Cooper, KSC, and Magnusson-Anissimov-Cross-Roberts, MACR, equations. The RS model which contains a parameter for the dependence of flux on solubility in water, SAQ, as well as solubility in the lipid isopropyl myristate, SIPM, gave the best fit: log JMMAQ = −2.30 + 0.575 log SIPM + 0.425 log SAQ − 0.0016 MW, r2 = 0.903. The values for the coefficients to the parameters are quite similar to those obtained when the RS model was fit to flux of solutes from water through human skin, log JMHAQ. There was no trend in predicting the under or over-performance of prodrugs based on their fit to the RS model and whether they were more or less soluble than their parent drugs. There was an inverse dependence of log JMMAQ on partition coefficients or permeability coefficients similar to that observed for log JMHAQ. The similarities in trends for results for log JMMAQ and log JMHAQ suggests that design directives obtained from mouse skin can be extended to design new prodrugs or select new drugs for delivery through human skin.