In vivo assessment of enhanced topical delivery of terbinafine to human stratum corneum

Purpose: The objective of this study was to evaluate, using attenuated tota l reflectance Fourier transform infrared spectroscopy, the stratum corneum (SC) bioavailability of terbinafine (TBF) following topical treatment with four different formulations. Methods: Four skin sites on the ventral forear ms of five healthy volunteers were treated for 2 h using one of four formul ations based on a vehicle consisting of 50% ethanol and 50% isopropyl myris tate. Three of these formulations included a percutaneous penetration enhan cer: either 5% oleic acid, 10% 2-pyrrolidone or 1% urea. The SC concentrati on profile of TBF was measured by repeated infrared spectroscopic measureme nts while sequentially stripping off the layers of this barrier membrane wi th adhesive tape. This method was validated by HPLC analysis of TBF extract ed from the stripped tapes. Transepidermal water loss (TEWL) measurements w ere also performed, to permit facile estimation of SC thickness. Results: T he SC concentration profiles of TBF were fitted to the appropriate solution of Fick's second law of diffusion, thereby allowing determination of the c haracteristic diffusion and partitioning parameters of the permeating drug. This analysis enabled the efficacies of the different formulations tested to he compared to the no-enhancer control. While it was found that the form ulation containing 5% oleic acid significantly enhanced the SC availability of TBF, the other formulations did not improve the apparent drug delivery. Conclusions: A facile and minimally invasive methodology to evaluate an im portant aspect of topical drug bioavailability has been described. The anal ytical methods used (infrared spectroscopy and HPLC) allow estimates of bot h relative and absolute drug bioavailability in the SC and may be useful, t herefore, in the critical determination of bioequivalence between topical f ormulations. (C) 2001 Elsevier Science B.V. All rights reserved.