42 JOURNAL OF COSMETIC SCIENCE ( 13.4 min) ot-TAc (16.0) min Spiked ot-T peak ( 13.9 min) o½-TAc peak I (16.3 min) Spiked ot-TAc peak (16.2 min) o½-T. pea.k • ( b peak .4 min) ot-T peak (13.3 min) Spiked ot-TAc peak ( 15.9 min) Spiked peak (13.8 min) Figure 2. HPLC chromatograms of viable skin sample (a) of an ot-TAc IPM-solution, (b) spiked with ot-TAc, (c) spiked with or-T, (d) of an ot-T (IPM-solution), (e) spiked with ot-TAc, and (0 spiked with ot-T.

PERMEATION AND METABOLISM OF c•-T and c•-TAc 43 100 n • • 90 •o • 80 ==-- 70 5 • 60 • • 50 40 0 10 20 30 Time (hrs) ß IPM solution! I Emulsion Figure 3. Amount unabsorbed (wash + two strips) for ot-TAc formulations. Values are percentage of applied dose, mean + SEM (n = 4). 12n I 8 10q --• 6 • • 2 IPM solution Emulsion ß Stratum comeurn [] alpha-TAc in viable skin [] AIpha-T in viable skin [] Total amount permeated Figure 4. Permeation profile at two hours. Values are percentage of applied dose, mean + SEM (n = 4). Figure 5 shows the permeation profile at six hours. A lower amount of c•-TAc was detectable in the stratum corneum at six hours than at two hours, but more was detected in the viable skin. The emulsion formulation showed higher amounts of total drug permeated than the IPM solution at six hours, and this difference was statistically significantly different (t-test, c• = 0.05). Figures 6 and 7 show permeation profiles at 12 and 24 hours, respectively. The amount of c•-TAc that permeated in the SC of the IPM solution at 24 hours was statistically significantly higher than at 2, 6 and 12 hours. The amount of prodrug permeated or metabolite formed in viable skin or the total amount of c•-TAc permeated at both 12 and 24 hours were not statistically significantly different between the two formulations. In terms of the total amount permeated for the IPM