PERCUTANEOUS ABSORPTION OF DRUGS 379 The (log P)• term in eq 7 is not statistically significant and the 95% con- fidence interval of log Po could not be defined. The molecular weight term (log MW) in eq 9 is significant at the 90 percentlie level as indicated by an F test (F•,4 = 7.01 F•,4o.9o ---- 4.54). SSk• - SS•2 (n - k2) /?k2-kl, n-k2---• SSk2 x (k2 - kl) n = number of data points, k• = number of coefficients in first equation = no. of variables + 1, k2 = number .of coefficients in second equation, SSk• = sum of squares of deviation from first equation, SSk2: suln of squares of deviations from second equation. The positive dependence on log P and the negative dependence on log MW or molar refraction (log MRa) in eqs 4-6, 8, and 9 suggest that small molecules with high lipid solubility will penetrate through the skin most rapidly. Similar linear equations are obtained for the penetration into rabbit dermis alone (eqs 10-12). Since only 6 data points are available, no addi- tional term is justifiable at the 90 percentile level. Comparing eq 6 with eq 10, one can see that the intercept of eq 10 is much higher than that of eq 6 (-0.970 vs. -2.761), indicating much higher permeability through dermis than through whole skin and reflecting the barrier effect of epidermis (Fig. 1). Equations 13-1.5 are derived from the permeability experiment on aliphatic alcohols through human epidermis by Scheuplein's group (14, 15), and eqs 16-22 are from similar experiments on steroids: log K• (cm/hr) = 0.420 log Ko - 2.354 (13) (n = 8, r = 0.977, s = 0.156) log K• (cm/hr) = 0.544 log P - 2.884 (14) (n = 8, r = 0.979, s = 0.150) log K• (cm/hr) = 0.934 log Km- 2.891 (15) (n = 8, r = 0.986, s = 0.121) log K• (cm/hr): 0.818 log K(•ex) - 3.556 (16) (n = 13, r = 0.865, s = 0.473) log K• (cm/hr) = 1.262 log K(,c) - 5.211 (17) (n = 13, r = 0.933, s = 0.339) log K• (cm/hr) = 2.626 log Km- 7.537 (18) (n = 14, r = 0.931, s = 0.377) log K• (cm/hr) = 0.891 log P'(ethex.) -- 5.175 (19) (n = 10, r = 0.964, s ----- 0.261)

380 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS "• 2.C -0.5 -1. o, LOG K m -/4.0 a -6.0 '7.0 Figure 2. Dependence of the permeability constant (log Kp) on the stratum corncure/wa- ter partition coefficient (log K•n). Eq i0 is derived from the data of alcohols absorbed through human epidermis eq 18 from data of steroids absorbed through human epidermis