196 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS particularly if skin is damaged in harvesting or is stored before use. The use of a standard compound such as tritiated water to check barrier integrity of the skin aids in the assessment of the accuracy of absorption measurements. No significant differences in the total absorption of AHAs at pH 3.0 were observed in either Tables II or IV. However, some differences in absorption were obtained in levels measured in the receptor fluid or skin locations. 2-Hydroxyhexanoic acid levels are much higher in the receptor fluid and lower in skin than other AHAs (Table II). The skin levels of 2-hydroxyoctanoic acid are lower than the other AHAs in Table IV. A different comparison of the AHA absorption values can be made by examining the percent of the absorbed dose remaining in the skin (Figure 5). It appears that there is a tendency toward a decrease in the percentage of the absorbed AHA remaining in skin and stratum comeurn (data not shown) with the longer-chain compounds. This is opposite to what might be expected for the more lipophilic compounds, especially 2-hydroxydecanoic acid. The octanol/water (pH 3.0) partition coefficients for 2-hydroxyhexanoic, 2- hydroxyoctanoic, and 2-hydroxydecanoic acids were determined to be 3.7, 30.6, and 71.1, respectively. However, these acids ionize to polar compounds at physiological pH as they enter and are absorbed through the stratum comeurn. The pH of human stratum comeurn in the diffusion cells was determined to range from initial surface values of approximately 5.3 up to values ranging from 6.5 to 7.3 at the stratum comeurn-viable epidermal interface (Figure 3). These values are in agreement with in vivo stratum comeurn stripping studies that found a pH gradient in human stratum comeurn ranging from pH 4.5 to 5.3 on the skin surface to a pH of about 7 at the viable epidermal layer (8). Therefore, these longer chain AHAs are not expected to form a reservoir in skin based on their lipid solubility properties. 100 r- 80 .m (1) 60 0 -Q 40 O • 20 [•1 Glycolic 5% kN%%%-• Lactic 5% • 2-hydroxyhexanoic 5% [•1 2 hydroxyhexanoic 0.5% ffTT1Trl 2-hydroxyoctanoic 0.5% • 2-hydroxydecanoic 0.5% Alpha Hydroxy Acids Figure 5. The effect of AHA chain lengths on skin levels. The values are the mean q- SEM of two to five determinations in each of three subjects.

ABSORPTION OF AHAs IN SKIN 197 The percutaneous absorption of GA through animal skin has previously been reported from an aqueous solution (9). Absorption values of 0.7% and 0.9% were reported in 8 h through minipig and hairless mouse skin, respectively, from a pH 3.8 aqueous solu- tion. But an infinite dose applied to skin of over 100 pl per cm 2 makes the values not relevant to "in use" conditions. We have found that AHAs are extensively absorbed into and through human skin from a relevant dose of an O/W emulsion adjusted to pH 3.0. Approximately 27% of the applied dose ofglycolic acid was absorbed in 24 h, and there was no significant difference in total absorption when compared with values obtained from longer-chain AHAs. REFERENCES (1) D. B. Hagan, D. T. Partort, and A. P. Taylor, A study of the structure-activity relationships present in skin active agents, Int. J. Cosmet. Sci., 15, 163-173 (1993). (2) J.j. Leyden, R. M. Lavker, G. Grove, and K. Kaidbey, Alpha hydroxy acids are more than moistur- izers,J. Geriatr. Dermatol., 3 (Suppl A), 33A-37A (1995). (3) R. M. Lavker, K. Kaidbey, and J. j. Leyden, Effects of topical ammonium lactate on cutaneous atrophy from a potent topical corticosteroid, J. Amer. Acad. DermatoL, 26, 535-544 (1992). (4) E.J. Van Scott and R.J. Yu, Alpha hydroxy acids: Procedures for use in clinical practice, Cutis, 43, 222-228 (1989). (5) R.L. Bronaugh and R. F. Stewart, Methods for in vitro percutaneous absorption studies. IV. The flow-through diffusion cdl,J. Pharm. Sci., 74, 64-67 (1985). (6) S. W. Collier, N.M. Sheikh, A. Sakr, J. L. Lichtin, R. F. Stewart, and R. L. Bronaugh, Maintenance of skin viability during in vitro percutaneous absorption/metabolism studies, Toxicvl. AppL PharmacoL, 99, 522-533 (1989). (7) R. L. Bronaugh, R. F. Stewart, and M. Simon, Methods for in vitro percutaneous absorption studies. VI. Use of excised human skin, J. Pharm. Sci., 75, 1094-1097 (1986). (8) H. •hman and A. Vahlquist, In vivo studies concerning a pH gradient in human stratum comeurn and upper epidermis, Acta Derre. Venereol. (Stockh.), 74, 375-379 (1994). (9) M. Goldstein and R. Brucks, Evaluation of glycolic acid permeation through skin, Pharm. Res., 11, S-180 (1994).