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J. Cosmet. Sci., 56, 91-103 (March/April 2005) Permeation study of five formulations of alpha-tocopherol acetate through human cadaver skin HANSA MAHAMONGKOL, ROBERT A. BELLANTONE, GRAZIA STAGNI, and FOTIOS M. PLAKOGIANNIS, Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, 75 DeKalb Avenue, Brooklyn, NY 11201. Accepted for publication February 16, 2005. Presented in part at the Annual Meeting of the American Association of Pharmaceutical Scientists, Baltimore1 November 7-111 2004. Synopsis Alpha-tocopherol (AT) is the vitamin E homologue with the highest in vivo biological activity. AT protects against the carcinogenic and mutagenic activity of ionizing radiation and chemical agents, and possibly against UV-induced cutaneous damage. For stability consideration, alpha-tocopherol is usually used as its prodrug ester, alpha-tocopherol acetate (ATA), which once absorbed into the skin is hydrolyzed to alpha­ tocopherol, the active form. The objective of this research was to characterize in vitro the permeation properties of ATA from various solutions and gel formulations. Permeation studies were conducted using modified Franz diffusion cells and human cadaver skin as the membrane. Specifically, 5% (w/w) alpha­ tocopherol acetate was formulated in the following vehicles: ethanol, isopropyl myriscate, light mineral oil, 1 % Klucel® gel in ethanol, and 3% Klucel® gel in ethanol (w/w). The receiver temperature was 37 ° C. Samples from the receiver were collected at 2, 4, 6, 8, 12, 24, 30, 36, and 48 hours and analyzed by HPLC for concentrations of alpha-tocopherol acetate and alpha-tocopherol. The permeabilities of ATA through human cadaver skin were 1.0 x 10-4, 1.1 x 10- 2 , 1.4 x 10-4, 2.1 x 10- 4 , and 4.7 x 10-4 cm/h for the ethanol solution, isopropyl myristate solution, light mineral oil solution, 1 % Klucel® gel, and 3% Klucel® gel, respectively. The results show that the formulation had relatively minor effects on the permeability coefficients of AT A through cadaver skin in all cases except for the isopropyl myristate solution. INTRODUCTION Alpha-tocopherol is the major lipophilic antioxidant in many biological systems (1). The main antioxidant function of AT is to prevent lipid peroxidation at the cell membrane site and therefore to promote the preservation of the structural integrity of the mem­ brane. AT is present in high concentration at the lower levels of the stratum corneum (2,3) where it represents the first line of defense of the skin from the oxidative stress of Address all correspondence to Fotios M. Plakogiannis. 91