Stability, Cutaneous Delivery, and Antioxidant Potential of a Lipoic Acid and α-Tocopherol Codrug Incorporated in Microemulsions

The aim of this study was to assess the skin penetration, stability, and antioxidant effects of a α-tocopherol-lipoic acid codrug. To enhance penetration, we evaluated three microemulsions varying in water content and composition of the oil phase (isopropyl myristate with either monocaprylin or oleic acid). The codrug was incorporated at 1% (w/w). Codrug hydrolysis in the microemulsion increased with increases in time (up to 48 h) and formulation water content (10%-30%, w/w). Microemulsions increased the codrug delivery into viable layers of porcine ear skin by 2.9-7.8-fold compared with a control formulation (20% monocaprylin in isopropyl myristate) after 24 h. Penetration enhancement was influenced by the oil phase, with the formulation containing monocaprylin displaying the most pronounced effect. Antioxidant activity, assessed in skin bioequivalents using the thiobarbituric acid-reactive substances (TBARS) assay, demonstrated that TBARS levels decreased by 39% after treatment with the codrug-containing microemulsion compared with the unloaded formulation. In addition to the codrug, tocopherol (8.2 ± 0.6 μg/cm2) was detected in the viable bioequivalent tissues, suggesting that the codrug was partly hydrolyzed after 12 h. Taken together, these results support the potential of nanodispersed formulations containing a tocopherol-lipoic acid codrug to improve skin antioxidant activity. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2530-2538, 2014