Effect of formulation on the delivery and metabolism of α-tocopheryl acetate
Meera Rangarajan , Joel L. Zatz

Synopsis

The effect of delivery system on the permeation and metabolism of α-tocopheryl acetate (α-TAc) was studied in micro-Yucatan pig skin, which closely resembles human skin. Various α-tocopheryl acetate formulations, including a simple isopropyl myristate (IPM) solution, an o\/w emulsion, microemulsions, which differed in their oily phase content, and alcoholic and hydroalcoholic gels were made. A suitable HPLC method was developed and validated to separate and quantify α-TAc and α-tocopherol (α-T). Dulbecco's modified phosphate-buffered saline with 3% bovine serum albumin (DMPBS-BSA 3%) served as the receptor media to ensure tissue viability and to maintain skin conditions. Finite doses (5 μl) of the formulations were applied to viable pig skin using a statistically approved randomized complete block design.

Data were analyzed using Tukey's studentized range test, and interday variability was estimated using an F-test. About 70% of the active was recovered from the wash, representing the amount adhering to the surface of the skin. α-TAc underwent metabolism in pig skin to the active antioxidant, α-T. The identity of the HPLC peaks were confirmed by spiking studies using known standards. The extent of metabolism was found to be formulation-dependent. No α-T was, however, detected in the stratum corneum. A higher extent of metabolism was obtained for the IPM solution, a microemulsion containing IPM as the oily phase, and the hydroalcoholic gel, when calculated based on the percent of total α-TAc permeated in the viable skin. Metabolism occurred in pig skin to the extent of 15–20% in terms of the total amount of α-TAc permeated in the viable skin and stratum corneum. Thus the topical delivery and metabolism of α-TAc were found to be dependent on formulation.

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