Normalization of stratum corneum barrier function and transepidermal water loss in vivo

PURPOSE : To understand and account for inter-individual variations in percutaneous drug penetration and transepidermal water loss (TEWL). METHODS: TEWL is the standard measure of stratum corneum (SC) barrier function in vivo. The use of serial tape-stripping enables SC barrier efficiency to be assessed as a function of position. Previous studies have shown that TEWL increases as the barrier is removed by progressive tape-stripping. Although complete removal of the SC results in TEWL increasing to 80-100 g/m2h, inter-individual (and inter-regional) differences in SC thickness mean that different amounts of tissue have to be removed before these TEWL levels are attained. RESULTS: We show that normalization of the amount of SC removed with respect to the total Sc thickness effectively eliminates the inter-individual differences perceived in the raw data (i.e., TEWL as a function of tape-stripping number or as a function of cumulative SC mass removed). CONCLUSIONS: The results of this study demonstrate clearly that the objective evaluation of topical drug bioavailability (or of topical bioequivalence between different formulations) using tape-stripping methodology, as has been recently advocated by the U.S. Food & Drug Administration, must involve a quantitative determination of the amount of SC removed. In this way, the significant inter-individual differences typically observed in the penetration measurements may be decreased