110 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 0,50 _ F ¸ 0,25 K ¸ = 0,050 ---- -'•- -- K ¸ = O, 010 ß o ß 5'- - -" • • K ¸ = O, 001 6 12 TIME/HRS, Figure 4. Case I: Zero-order surface loss. Time-dependence of F ø, the fraction of the applied dose lost from the surface due to the K ø process. The value of K ø corresponding to each curve is indicated. Calculation of these curves utilized equation 17. U o 0,5 \ C•SE, K I, K1 •1• .... I IA, O, 100, O, 036 IIc, 0,200, 0,036 --__liB, 0,100, 0,180 0 I 0 6 12 IID, 0,200, 0,180 TIME/HRS, Figure 5. Case II: First-order surface loss. Concentration-time profiles (calculated using equation 13) for %, the surface concentration of topically applied agent. The combinations of rate constants used for each profile are identified in the figure and listed in Table I.

PERCUTANEOUS ABSORPTION KINETICS 111 ! u 1 0,04 \ \ \ 0 I CASE K I K1 ß ß IIBß O,lOOj 0,]80 IIDj 0,200ß 0,180 2.. -Q'-'-2_l.a.-----' IIAj 0,100ß 0,036 • IIc. 0,200ß 0,036 0 6 12 TIME/HRS, Figure 6. Case II: First-order surface loss. Concentration-time profiles (calculated using equation 14) for u•, the stratum corneum concentration of agent. The combinations of rate constants used for each profile are identified in the figure and listed in Table I. The fraction (F •) of the applied dose lost from the surface due to the k I process is also assessed. The calculation requires the integration of equation 10 in which (k I + k•) is replaced by k I only. The result is equation 18: k I k I F• - k • + k• (1 - exp[-(k I + k0t]) - k• + k• (1 - u0) (18) The form of this equation is sensible since it shows that as u0 (the concentration of agent in the applied surface film) goes to zero, which corresponds to long times, F • approaches k•/(k • + k0, i.e., Amount lost to k • process FIu0_•0 Amount lost to k • process + amount lost to k• process Amount removed from surface Amount removed from surface + amount absorbed into skin . F • profiles for the four permutations of k • and k• are shown in Figure 7. In Table I, for Case II situations, the values of t90 (corresponding to u0 = 0.1) are presented.