ALPHA-TOCOPHEROL ACETATE PERMEATION 300 0 500 ti .:. Cl) cu Cl) 0 14000 - r:: ( Cl) cu 0 ::::, 0 1000 0 2000 0 Ethanol Solution / / . . /· � Light Mineral Oil � +/· � lsopropyl Myristate T v-� T/.l. ♦ / ♦-....�� 1% Klucel Gel 4 � � .� �•--- 3% Klucel Gel 50 Time (hr) 101 Figure 2. Cumulative amount release vs time for the five formulations tested. The diamonds ( ♦) represent the experimental data and the solid line the fit using equation 1. The error bars represent ± the standard deviation (n = 3). For the ethanol and mineral oil solutions the error bars are too small to be seen. nature of the stratum corneum (11). This property would make isopropyl myristate thermodynamically similar to the stratum corneum and would facilitate the permeation of ATA through the skin. It is also known that water, which is present at the surface of

102 10000 Q 5000 D JOURNAL OF COSMETIC SCIENCE 10 20 30 40 50 Time (hl'II) Figure 3. Cumulative amount released vs time for the diffusion of AT A from isopropyl myristate through human cadaver skin. Diamonds ( ♦ ): experimental data. Dashed black line: fit by model case 1. Solid gray line: fit by the lag-time model. the skin and in the skin itself, can create a resistant boundary at the donor-skin interface and may prolong or delay the permeation of poorly water-soluble molecules. AT A has to dissolve in this water layer before reaching the skin, and the presence and thickness of this layer would affect the permeability. For the alcoholic gels, it is possible that the gelling agent absorbs the water present on the skin membrane and therefore reduces the time to permeate into the skin, as can be seen from the shorter lag time as the percent of the Klucel® agent increases (12, 8, and 2 hours for the ethanol solution and the 1 % and 3% Klucel® formulations, respectively). However, reduction of the water layer is not sufficient to promote substantial penetration into the skin. AT A released from the ethanol solution and 1 % and 3% Klucel® didn't differ significantly, as shown in Figure 2 or by the values of the permeability coefficients. The light mineral oil solution has a permeability similar to that of the ethanol formulations. It is possible that the layer of water at the interface between the formulation and the skin would be thicker because of the incapability of mineral oil to absorb it, and it would contrast the facilitating effect due to the similarity between the lipid bilayer of the stratum corneum and the light mineral oil. CONCLUSION Permeability studies performed on five different formulations of ATA show that iso­ propyl myristate favors the highest permeability through human cadaver skin in the experimental conditions tested in this study. There was not a statistically significant difference between the permeabilities of the other formulations, suggesting that the formulation had relatively minor effects on the permeation of AT A. Further studies are necessary to confirm these findings in vivo. ACKNOWLEDGMENTS This research is reported in part in the Master's Thesis of Hansa Mahamongkol and was performed in partial fulfillment of the requirements for the degree of Master in Cosmetic Sciences in the Division of Pharmaceutical Sciences at the Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY. The authors express thanks to Novartis (Somerville, NJ) for the donation of the human