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 the topical drug terbinafine (TBF) in human stratum corneum (SC) in vivo following its administration in formulations containing isopropyl myristate and ethanol.

METHODS

The ventral forearms of human volunteers were treated for 4 h with TBF, at a concentration equal to 1/4 saturation, in isopropyl myristate (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 subsequent HPLC analysis; and (b) attenuated total reflectance infrared spectroscopy (ATR-FTIR) of each sequentially exposed SC surface during the tape stripping 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 thereby the drug's SC/vehicle partition coefficient (K) and characteristic diffusion parameter (D/L(2), where D is the diffusivity of TBF in the SC of thickness L) to be deduced.

CONCLUSIONS

While D/L(2) for TBF derived from the three 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 supported these deductions.