PERCUTANEOUS ABSORPTION OF LACTIC ACID 263 20 * p0.01 pH 3.8 • pH ?.0 T - 40 E 30 ::t. 20 '• 10 =• o o Corneum Epidermis Dermis Tissue deposition Figure 2. Tissue deposition of lactic acid six hours after application of a 2-pl finite-dose o/w emulsion film at pH 3.8 and pH 7.0 (n = 7). Values are mean (n: 7) _+ standard error of mean (SEM). The cumulative receptor penetration at six hours at pH 3.8 is 0.3% -+ 0.1 SEM and that at pH 7.0 is 0.2% _+ 0.0 SEM. effects of differences in time points and cells. The cumulative receptor flux profiles as a function of time for the two application modes are compared in Figure 5. In the infinite-dose situation, a steady state was reached within two hours. The epidermal and dermal concentrations of lactic acid six hours after application of an oil-in-water emulsion are shown in Table II. The tissue concentrations are calculated based on epidermal and dermal thicknesses of 48 and 448 pm, respectively. The data shows that it should be possible to deliver mMolar level of AHA in the living skin tissues from a typical cosmetic rub-on product. Enhanced epidermal cell turnover by lactic and glycolic acid has been suggested (9) as a possible mechanism for their anti- aging efficacy. The results presented here suggest greater bioavailability of ot-hydroxy acids in the SC and epidermis at acidic conditions, which may lead to higher efficacy. However, these in vitro observations need to be validated with in vivo measurements. A comparison of the finite- and infinite-dose delivery data (Figures 2 and 3) shows that the finite-dose film delivered more lactic acid to the stratum corneum and comparable amounts to the epidermis. The greater efficacy of the finite-dose film is a consequence of a rapid increase in the active concentration in the applied film following application due to evaporation of water. The results highlight the fact that the changes in the thermodynamic activity of the active in a finite-dose film can often be a significant factor in active delivery to skin (19). EFFECT OF PROPYLENE GLYCOL The effect of 5% propylene glycol (PG) as a penetration enhancer for lactic acid from

264 JOURNAL OF COSMETIC SCIENCE 0.9 0.3- 0.0 i i pH 3.8 • pH 7.0 Corneum Epidermis Dermis Tissue deposition diff. not sig. p=0.12 - 120 - 100 - 80 • - 60 ,• - 40 • - 20 0 Figure 3. Tissue deposition of lactic acid six hours after application of a 75-pl o/w infinite-dose emulsion at pH 3.8 (n = 6) and pH 7.0 (n = 7). Error bars represent SEM. The cumulative receptor penetration at six hours at pH 3.8 is 0.01% +_ 0.01 SEM and that at pH 7.0 is 0.01% + 0.0 SEM. oil-in-water emulsions was investigated. The low concentration of propylene glycol used in this study is typical of PG levels in cosmetic products containing tx-hydroxy acids. The tissue concentrations for infinite-dose and topical film are shown in Figures 6 and 7, respectively. The time dependency of the transdermal penetration of lactic acid in the infinite-dose situation, assessed by the cumulative absorption in the receptor phase, is shown in Figure 8. Propylene glycol is more efficacious in the infinite-dose situation. It significantly en- hances the active level in the tissue fractions (Figure 6) as well as in the receptor fluid (Figure 8). This is expected, as the penetration enhancement effect is related to the amount of loading of the enhancer. However, significant enhancement of lactic acid delivery to viable epidermis was observed even for consumer-relevant topical-film ap- plication (Figure 7). It remains to be seen whether such enhancement could be correlated with the greater anti-aging efficacy of the formulation. EFFECT OF PRODUCT STRUCTURE The in vitro percutaneous absorption of lactic acid from the o/w, w/o, and w/o/w emul- sions was determined using topical application of 2-pl product film. The amounts in