PERCUTANEOUS ABSORPTION OF LACTIC ACID 265 0.05 0.04 0.03 0.02 O.Ol 0.00 -- pH 3.8 -- pH 7.0 0 1 2 3 4 5 6 0.25 - 0.20 - 0.15 - 0.10 - 0.05 0.00 Time (hours) Figure 4. Receptor phase flux profiles of lactic acid delivered from a 2-1al o/w emulsion film at pH 3.8 (n = 6) and pH 7.0 (n = 7). Error bars represent SEM. different tissue compartments are shown in Figure 9. The total deposition and absorp- tion of lactic acid as a percent of applied dose was in the order of o/w w/o/w w/o. Compared to the w/o emulsion, the o/w emulsion delivered significantly more (p 0.05) lactic acid to all the tissue fractions. Compared to the w/o/w emulsion, the o/w emulsion delivered significantly more (p 0.02) to the SC and dermis and directionally more to the viable epidermis. The receptor-phase flux profiles were significantly different with the three different emulsions (Figure 10). With o/w emulsion, receptor flux went through a maximum in about three hours, whereas with the other two emulsions, the flux increased to a plateau after one hour. It should be noted that in most of our studies with o/w emulsion, the maximum in the receptor flux occurs within the first hour. The receptor fluxes for w/o and w/o/w emulsions were nearly identical. DISCUSSION Percutaneous absorption of lactic acid to tissue compartments can be enhanced by acidic pH and propylene glycol. However, the effects of these formulation changes depend strongly on the mode of application, i.e., finite or "infinite" dose. The percutaneous absorptions of lactic acid for the two application modes are qualitatively as well as quantitatively different.

266 JOURNAL OF COSMETIC SCIENCE • 2 T 2 gl finite dose 75 •tl infinite dose 0 I I I 0 1 2 3 4 5 6 Time (hours) Figure 5. Time dependency of transdermal penetration of lactic acid delivered from a 2-pl finite-dose o/w emulsion film (n = 6) and a 75-pl o/w infinite dose (n = 7) at pH = 3.8 as assessed by the cumulative absorption in the receptor phase. Error bars omitted for clarity. These penetration results suggest that the penetration pathways for lactic acid in the corneum for the topical-film and infinite-dose applications might be different. In the finite-dose situation, the SC, except for a short (ca 20 minutes) period following appli- cation, was not hydrated. Thus the active has to penetrate the corneum through a hydrophobic (possibly the lipid) pathway. At pH 3.8, lactic acid is 50% ionized (pK a = 3.8), whereas at pH 7.0, it is 99.9% ionized. It is known that charged species penetrate poorly through the hydrophobic lipid bilayers. These results are in agreement with in vitro measurements by Michaels et al. (20), which suggest that the permeabilities of the ionized forms were -1/20 of those for their un-ionized forms. Assuming that stratum corneum is the principal barrier to lactic acid penetration, the permeability coefficient, P, can be calculated from the receptor flux, J, from the fol- lowing equations (22):