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

• Published in: Journal of controlled release Vol. 71; no. 3; pp. 319 - 327
• Main Authors: Alberti, Ingo, Kalia, Yogeshvar N., Naik, Aarti, Bonny, Jean-Daniel, Guy, Richard H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28.04.2001; Elsevier
• Subjects: 2-pyrrolidone; Administration, Topical; Adult; Algorithms; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - administration & dosage; Antifungal Agents - pharmacokinetics; Antimycotics; Biological and medical sciences; Diffusion; Female; Fourier transform infrared spectroscopy; General pharmacology; Humans; Male; Medical sciences; Middle Aged; Naphthalenes - administration & dosage; Naphthalenes - pharmacokinetics; oleic acid; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Skin Absorption; Spectroscopy, Fourier Transform Infrared; Tape stripping; terbinafine; Topical administration; Topical bioavailability; urea; Tape stripping; Topical bioavailability; Fourier transform infrared spectroscopy; Antimycotics; Topical administration; Human; Stratum corneum; Pharmaceutical technology; Ethanol; Healthy subject; Allylic compound; Terbinafine; Percutaneous route; Colloidal gel; Antifungal agent; Amine; Myristic acid; Dosage form; Skin; Absorption enhancer; Pharmacokinetics; Transepithelial transport
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(01)00244-9

Purpose: The objective of this study was to evaluate, using attenuated total 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 forearms of five healthy volunteers were treated for 2 h using one of four formulations based on a vehicle consisting of 50% ethanol and 50% isopropyl myristate. Three of these formulations included a percutaneous penetration enhancer: either 5% oleic acid, 10% 2-pyrrolidone or 1% urea. The SC concentration profile of TBF was measured by repeated infrared spectroscopic measurements while sequentially stripping off the layers of this barrier membrane with adhesive tape. This method was validated by HPLC analysis of TBF extracted from the stripped tapes. Transepidermal water loss (TEWL) measurements were also performed, to permit facile estimation of SC thickness. Results: The SC concentration profiles of TBF were fitted to the appropriate solution of Fick’s second law of diffusion, thereby allowing determination of the characteristic diffusion and partitioning parameters of the permeating drug. This analysis enabled the efficacies of the different formulations tested to be compared to the no-enhancer control. While it was found that the formulation 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 important aspect of topical drug bioavailability has been described. The analytical methods used (infrared spectroscopy and HPLC) allow estimates of both relative and absolute drug bioavailability in the SC and may be useful, therefore, in the critical determination of bioequivalence between topical formulations.