PREDICTING PERCUTANEOUS ABSORPTION 409 Table IV Effect of Vehicle Composition on Percutaneous Absorption of Benzoic Acid in the Hairless Rat Maximum Total amounts found 96 h after application solubility of benzoic Epidermis acid in + dermis the vehicles area Animal Total Vehicles (mg/ml) Urine Feces treated body penetration Amounts in stratum corneum of the treated area 30 min after application Propyleneglycol- 219.5 0.81 a 0.32 0.03 0 1.15 0.73 triton x 100 (90/10) (0.08) b (0.09) (0.007) (0.12) (0.07) Glycerol-triton 28.5 1.57 0.59 0.04 0 2.20 0.91 x 100 (90/10) (0.31) (0.27) (0.006) (0.44) (0.10) Ethyleneglycol- 130.5 4.18 0.38 0.12 0.02 4.71 3.10 triton x 100 (90/10) (0.74) (0.12) (0.05) (0.009) (0.85) (0.55) [(Ethyleneglycol- 6.5 4.45 0.48 0.16 0 5.10 3.91 triton X 100) (0.48) (0.14) (0.04) (0.51) (0.31) (90/10)]-[water] (40/60) [(Propyleneglycol- 17.5 8.61 0.80 0.38 0.03 9.81 4.41 triton X 100) (1.14) (0.23) (0.08) (0.01) (1.33) (0.23) (90/10)]-[water] (40/60) Ethanol-water 220 24.80 1.32 0.50 0.01 26.60 17.60 (95/5) (0.50) (0.30) (0.05) (0.004) (0.65) (1.50) Methanol-water 19 30.46 2.50 0.88 0.18 34.02 18.68 (40/60) (2.93) (0.47) (0.10) (0.10) (3.01) (1.86) Ethanol-water 148 43.42 3.98 1.02 0.09 48.52 23.56 (60/40) (3.97) (0.36) (0.27) (0.03) (3.57) (3.43) Ethanol-water 40 49.56 3.59 0.78 0.15 54.08 28.39 (40/60) (4.95) (0.39) (0.12) (0.02) (5.21) (1.73) Expressed in nanomoles ß cm -2 application area S.D.: (n = 6). ß [] i so- 200 • 4o- z_ 115o • 8 [ •oo _ o le=• 20- o• I so -• o ß ß D O I 2 3 4 5 6 ? 8 9 Figure 9. Comparative values of solubility of benzoic acid in the vehicles and corresponding percutaneous absorption levels. 1: propyleneglycol-triton x 100 (90/10). 2: glycerol-triton x 100 (90/10). 3: ethylene- glycol-triton x 100 (90/10). 4: (ethyleneglycol-triton x 100) (90/10)-water (40/60). 5: (propyleneglycol- triton x 100)(90/10)-water (40/60). 6: ethanol-water (95/5). 7: methanol-water (40/60). 8: ethanol-water (60/40). 9: ethanol-water (40/60).

410 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS o o z z 50 40 30 ÷ 20- 10- NANOMOLES IN THE STRATUM CORNEUM AFTER 30 MINUTES OF CONTACT Figure 10. Influence of the tested vehicles on the relationship between the penetration level of benzoic acid within four days and its concentration in the stratum corneum at the end of application (30 min). can therefore be predicted by simply stripping the treated area and measuring the amount in the stratum corneum at the end of application. INFLUENCE OF ANATOMIC SITE* Although all authors agree on the importance of anatomic location in percutaneous absorption, the literature contains relatively little information on the subject. Further- more, general reviews dealing with this topic (23,27,28) often give contradictory expla- nations of the differences in permeability observed from one site to another. Moreover, if it is clear that both in vitro (27) and in vivo (29-31) the anatomical location is of great importance, the connection between the differences observed, the structure of the skin, and the physicochemical nature of the penetrant remain obscure. Percutaneous absorption of four radiolabeled compounds, (Carboxyl z4C) acetylsalicylic * This study was performed in collaboration with Pr. Howard I. Maibach, University of California, San Francisco.