402 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 0.5 -0.5 -1 -1.5 i I [ [ ] [ I i •o to 50 •o 70 no 9o • R.H. el 20 C Legend ß BEFORE [3 AFTER WATER ß AFTER HCA Figure 1. Dependence of human stratum corneum extensibility on ambient relative humidity. EFFECT OF pH The dependence of skin extensibility, penetration, and sorption on pH of the HCA solution is shown in Table I. The decrease in extensibility with increasing pH agrees with the previously reported observation that significant increases in extensibility are only obtained at low pH (7). Table I Effects of 0.2 mol D-• HCA Solution pH on Epidermis Extensibility and HCA Penetration Through and Sorption by Stratum Corneum Mean Mean Mean Sorption x 102 Extensibility Permeability constant, (moles/g stratum pH (adjusted Ratio (+_2 X S.E.) kp X 10 7 (ms -1, +-half corneum, +2 X S.E.) with TEA) at 20øC/65% RH range) at 30øC at 30øC --2.4 5 (+2) 1.7 (_+0.1) 2.0 (+--0.1) 3.0 5 (+- 1) 0.5 (-+0.3) 0.99 (+ 0.1) 3.5 3.9 (+0.7) -- -- 4.0 2.6 (+0.3) 1.34 (+0.02) 0.49 (+0.02) 5.0 1.3 (+-0.2) 0.3 (+0.3) 0.10 (+ 0.01) 6.0 1.0 (+0.2) Negligible • 0.08 (+-0.02) 6.8 1.2 (+ 0.2) Negligible a 0.034 (+ 0.005) b Steady-state penetration not achieved after 30 hours. Different skin donor.

SKIN PLASTICISATION BY 2-HYDROXYOCTANOIC ACID 403 Penetration and sorption also decrease as the pH increases. This is consistent with the general observation that unionised molecules have a higher stratum corneum:water par- tition coefficient than their ionised counterparts (14). The higher sorption at low pH, where HCA is essentially unionised, leads to an increase in the penetration rate as expected from Fick's first law of diffusion (12). The higher sorption of HCA at low pH also produces a greater extensibility increase, proba• ,, due to the higher equilibrium concentration of HCA in the skin. It thus appears that the pH dependence of extensibil- ity is simply a consequence of altering the concentration of undissociated HCA. This is shown clearly in Figure 2 in which extensibility is shown to be approximately linearly dependent on the free acid concentration in the vehicle calculated from a pKa value of 3.85 measured by other workers in this laboratory. EFFECT OF ADDITIVES The data in Table I suggest that increases in penetration and/or sorption (e.g., due to the presence of penetration enhancers) may be paralleled by an increase in extensibility. As a result, we have carried out a more complete investigation of the effect of a range of o 2.5 I ! I I 0.04 0.08 0.12 0.16 FREE ACID CONCENTRATION (mol 1-1) Figure 2. Dependence of epidermis extensibility on free acid concentration in solution. Initial HCA con- centration = 0.2 tool 1-•, pH adjusted with triethanolamine.