PERCUTANEOUS ABSORPTION OF LACTIC ACID 269 0.18 0.16 0.14 0.12 im 0.10 0.08 0.06 0.04 0.02 0.00 TLAG ß 75 gl o/w with PG ß 75 gl o/w without PG I I I I 0 1 2 3 4 5 6 20 • 15 • Y. o Time (hours) Figure 8. Transdermal penetration of lactic acid delivered from a 75-pl infinite-dose o/w emulsion at pH 3.8 with (n = 6) or without (n = 7) propylene glycol as assessed by the cumulative absorption in the receptor phase. Error bars represent SEM. ficient was 6.8 x 10 -6 cm/hour. This is similar to the permeability of glucose (15) and amino acids (18) in SC. The diffusivity, D, of lactic acid in the corneum could be calculated using the following equation (22): L 2 T•,AG -- 6D (3) where the lag time, Tz, AO is the x-axis intercept of the slope of the flux curve. From Figure 5, the lag time, Tz,AO was calculated as 1.276 hours. Assuming a stratum corneum thickness of 15 microns, the diffusion coefficient of lactic acid in corneum was calculated as 8.16 x 10 -• cm2/sec, which is similar to the diffusivity of nonionic molecules through stratum corneum (22). Such small diffusivity values for transport through aqueous pores might be due to small pore size or constriction in the pores. Propylene glycol significantly enhanced lactic acid penetration when delivered from an o/w emulsion in the infinite-dose situation. The analysis of the receptor flux data for the

270 JOURNAL OF COSMETIC SCIENCE 18 o • o/w w/o/w w/o - 40 - 35 • Comeurn Epi Dermis Receptor Tissue deposition Figure 9. Comparison of deposition of lactic acid six hours after application of a 2-1al finite-dose film of o/w, w/o, and w/o/w multiple emulsions (n = 7) at pH 3.8. Error bars represent SEM. infinite-dose situation (Figure 8) shows that 5% PG increased lactic acid permeability by about 85%. From the steady-state slopes, the fluxes were calculated as 2.4 and 1.3 lag/cm2/hr with or without PG. This leads to permeability values of 13.5 x 10 -6 and 7.3 x 10 -6 cm/hour with and without PG, respectively. The calculations were done assum- ing a donor-side lactic acid concentration in the aqueous phase of 0.1778 gm/ml (equiva- lent to 8% in the emulsion). Propylene glycol can enhance active penetration in a number of different ways. Depend- ing on the active and the mode of application, PG may enhance penetration by increas- ing active partitioning into skin and/or by increasing active diffusivity through the SC (23). As discussed earlier, the lack of pH dependance suggests that lactic acid when delivered from an infinite-dose o/w emulsion penetrates the hydrated corneum through water-filled pores. In that case, it is unlikely that active partitioning plays any role in active penetration through corneum. On the other hand, flux data (Figure 8) indicate that PG did not change the lag time (which for a given SC thickness is inversely proportional to the active diffusivity in the corneum) for lactic acid to reach the steady state. However, it is possible (24) that the hygroscopic nature of propylene glycol may