Effect of ethanol and isopropyl myristate on the availability of topical terbinafine in human stratum corneum, in vivo

Purpose: The objective of this study was to determine the availability of t he topical drug terbinafine (TBF) in human stratum corneum (SC) in vivo fol lowing its administration in formulations containing isopropyl myristate an d ethanol. Methods: The ventral forearms of human volunteers were treated f or 4 h with TBF, at a concentration equal to 1/4 saturation, in isopropyl m yristate (IPM), in ethanol (EtOH) and in 50:50 v/v IPM/EtOH. At the end of the application period, the treated sites were carefully cleaned of excess vehicle and the SC was progressively removed by sequential tape stripping. TBF was quantified in the SC by: (a) extraction of the tape strips and subs equent HPLC analysis; and (b) attenuated total reflectance infrared spectro scopy (ATR-FTIR) of each sequentially exposed SC surface during the tape st ripping procedure. Results: The concentration profile of TBF in the SC (i.e . drug concentration as a function of depth in the membrane) was fitted to the appropriate solution of Fick's second law of diffusion, allowing thereb y the drug's SC/vehicle partition coefficient (K) and characteristic diffus ion parameter (D/L-2, where D is the diffusivity of TBF in the SC of thickn ess L) to be deduced. Conclusions: While D/L-2 for TBF derived from the thr ee vehicles remained essentially constant, the drug's partitioning into the SC was significantly higher from formulations containing ethanol. Both the semi-quantitative infrared data and the more rigorous HPLC results support ed these deductions. (C) 2001 Elsevier Science B.V. All rights reserved.