TOPICAL DELIVERY OF ot-TOCOPHEROL 173 salicylate to study the transdermal delivery of sex hormones. Octyl salicylate gave the highest enhancement ratio, and other penetration enhancers like oleic acid and lauro- capram gave slightly lower ratios, albeit better than the control. We did not find oleic acid to significantly enhance the permeation of ot-T. A major reason for this difference could be the lipophilicty of the ot-T molecule. ot-T is a lipophilic compound (octanol/water partition coefficient = 480), log (P) = 2.68. A log (P) 2 is a good indicator of a highly lipophilic molecule. When 1-menthol along with ethanol was used as a penetration enhancer for benzoic acid and its 4-alkyl substituents, Kitagawa and Li (16) found increased permeability for benzoic acid but decreased values for the higher alkyl substituents. The addition of alkyl groups made the parent molecule more lipophilic. Further analysis showed that addition of enhancers made the skin relatively more hydrophilic compared to the vehicle, which induced an increase in the permeability coefficient of benzoic acid and decreases in those of its lipophilic substitu- ents. The effect of penetration enhancers on the permeation of [3-blockers was studied (30). The authors found azone to be a better enhancer than oleic acid. Their effects were found to be more pronounced with hydrophilic drugs than with lipophilic [3-blockers. The increment of lipid fluidity and the resulting enhanced water permeability is thought to be the reason for this phenomenon. Possibly in our study the high lipophilicity of ot-T was responsible for the lack of effect of oleic acid. Pig skin is a suitable model for carrying out in vitro permeation studies of ot-T and other antioxidants. However, we noticed that although studies carried out on the same piece of pig skin are comparable when pig skin was changed, there is a possibility of a variation in values, though the general trend tends to remain the same. Thus pig skin serves as a good indicator of the effect that may be obtained with different formulations, but further in vivo studies are required to arrive at definite conclusions. In summary, we have shown that topical application of ot-T significantly increased its concentration in skin and receptor fluid. High amounts of the active permeated in the receptor from a hydroalcoholic gel. Dose proportionality was observed when different concentrations of ot-T (up to 4%) were applied to the skin. We have shown that micro-Yucatan pig skin is a suitable model to study the effect of formulation factors on the permeation of actives. There are differences obtained between each piece of skin with respect to permeation. However, the general trend observed with the formulations is maintained. An IPM-containing microemulsion served as an effective delivery vehicle for ot-T. Oleic acid did not significantly enhance the permeation of or-T, probably due to the mechanism of action of oleic acid and the lipophilicity of ot-T. REFERENCES (1) M.G. Traber and H. Sies, Vitamin E in humans--Demand and delivery, Annu. Rev. Nutr., 16, 321-347 (1996). (2) B.N. Ames, Dietary carcinogens and anticarcinogens: Oxygen radicals and degenerative diseases, Science, 221, 1256-1264 (1983). (3) H. L. Gensler, M. Aicken, Y-M. Peng, and M. Xu, Importance of the form of topical vitamin E for prevention of photocarcinogenesis, Nutr. Cancer., 26, 183-191 (1996). (4) D. L. Bissett, G. G. Hillerbrand, and D. P. Hannon, The hairless mouse as a model of skin photoaging: Its use to evaluate photoprotective materials, Photodermatology, 6, 228-233 (1989). (5) P. Mayer, The effects of vitamin E on the skin, Cosmet. Toiletr., 108, 99-109, (1993). (6) K. Furuse, Vitamin E: Biological and clinical aspects of topical treatment, Cosmet. Toiletr., 102, 99-116 (1987).

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