412 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS BenzoJc •:id Acety{ sodium salt Caf rein Benzoic ac•d salicylic acid Among the numerous studies on the relationship between skin permeability and ana- tomic site, considerable attention has been given in recent years to finding favorable "windows" for transdermal treatment of systemic diseases. For various reasons, the post- auricular area has been studied most often for scopolamine transdermal drug delivery (38,39). According to Taskovitch and Shaw (40), the closeness of the capillaries to the surface of the skin may promote resorption of substances and give the postauricular skin its good permeability. As our results show (Figure 11), whatever the material applied, this area has a high level of permeability. Apart from caffeine, its permeability is significantly higher than that of the arm or abdomen and often similar to that of the forehead. As Table V and Figure 12 show, the correlation between the amounts of substance present in the stratum corneum at the end of a 30-min application and the total amount absorbed within four days is confirmed in man, whatever the factors involved in differ-

PREDICTING PERCUTANEOUS ABSORPTION 4 13 Table V Percutaneous Absorption of the Test Molecules According to Anatomic Site in Man Anatomic site Amount in Total amount urine after penetrated within 24 hours (A) 4 days (B) Amount in stratum corneum 30 minutes after application Predicted penetration within 4 days Compound.' benzoic acid sodium salt Vehicle: (ethyleneglycol/triton x 100) (90/10) n = 6 Arm (upper, outer) 3.02 (0.34) 6 Abdomen 5.73 (0.54) 6 Postauricular 7.54 (0.62) 8 Forehead 9.31 (1.76) 4.02 2.83 4.67 (0.45) (0.58) (1.07) 7.65 4.04 6.88 (0.72) (0.98) (1.80) 10.06 6.29 11.02 (0.82) (0.93) (1.72) 12.32 5.94 10.34 (2.30) (0.99) (1.81) (B) Calculated from urinary excretion: (B) - (A) 0.75 Compound.' cafj•ine Vehicle: [(ethyleneglycol/triton x 100) (90/10)]/[H20] [50/50] n = 7 Arm (upper, outer) 6.04 (0.92) 6 Abdomen 3.76 (0.67) 7 Postauricular 5.87 (0.52) 6 Forehead 11.17 (1.20) 12.09 6.75 11.83 (1.84) (0.84) (1.53) 7.53 4.31 7.36 (1.34) (0.60) (1.11) ll.72 7.46 13.13 (1.05) (1.24) (2.26) 22.35 11.60 20.71 (2.39) (1.52) (2.79) (B) Calculated from urinary excretion: (B) - (A) 0.5 Compound.' benzoic acid Vehicle: (ethyleneglycol/triton x 100) (90/10) n = 8 Arm (upper, outer) 6.87 (0.75) 7 Abdomen 10.88 (1.23) 8 Postauricular 16.87 (3.85) 7 Forehead 20.10 (2.39) 9.15 5.70 9.90 (1.01) (0.58) (1.00) 14.51 7.89 13.92 (1.64) (1.12) (1.97) 22.49 10.53 18.75 (5.14) (0.63) (1.15) 26.80 13.20 23.63 (3.19) (2.70) (4.79) (B) Calculated from urinary excretion: (B) - (A) 0.75 Compound.' acetylsalicylic acid n = 7 Arm (upper, outer) 6 Abdomen 6 Postauricular Vehicle: (ethyleneglycol/triton x 100) (90/10) 5.27 17.00 11.99 21.42 (0.18) (0.37) (1.34) (2.45) 5.34 17.20 9.98 17.74 (1.03) (3.35) (1.98) (3.62) 11.04 29.2 14.56 26.10 (2.50) (5.37) (1.30) (2.38) (continued)