SOLVENT SKIN INTERACTIONS 331 io I I I Cs/, Cs/ Cs Benzocaine Conc. Figure 2. Effect of benzocaine concentration on mean value of penetration flux through polypropylene membrane from aqueous solution. Bars indicate standard deviation. from the receptor solution through the membrane. Precipitation was not observed in any of the solvents when excised hairless mouse skin was utilized. Values of Js were calculated from the slope of these plots. Results are listed in Table I. Based on our knowledge of this membrane, we anticipated that interactive effects would be negligible, and therefore the three values of Js for this membrane should be the same. Indeed, they are rather close to each other, differing by less than a factor of two, while the solubility values differ by a factor of as much as 300 times. Water flux from the receptor into the donor would lower the solubility of benzocaine in propylene glycol and polyethylene glycol 400, so that benzocaine activity in these solvents would be higher, accounting for the slightly higherJs value for benzocaine in these solvents than in water. The similarity of the Js values is taken as confirmation of the validity of our approach. x 90 u LL. 30 Benzocaine Conc. Cs Figure 3. Effect of benzocaine concentration on mean value of penetration flux through hairless mouse skin from propylene glycol solution.

332 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Cs/• Cs Benzocaine Conc. Figure 4. Effect of benzocaine concentration on mean value of penetration flux through hairless mouse skin from polyethylene glycol 400 solution. Penetration plots for excised hairless mouse skin were also linear. Flux was calculated for the linear portion, and values for each system were averaged. Figures 3 to 5 describe the relationship between mean flux of benzocaine through hairless mouse skin and donor concentration. The curves for propylene glycol (Figure 3) and polyethylene glycol 400 (Figure 4) were linear, but that for the aqueous solutions (Figure 5) was not. In Figure 5, the ratio of flux to donor concentration increases with concentration. The difference in flux between a saturated solution containing excess solid benzocaine and 120 9O 6O Cs/e Cs/a Benzocaine Conc. c s Figure 5. Effect of benzocaine concentration on mean value of penetration flux through hairless mouse skin from aqueous solution. ß solution O saturated solution containing excess benzocaine.