1. ¹School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland
2. ²Centre Pharmapeptides, Parc d'affaires International, Archamps, France
3. ³The School of Pharmacy, University of London, London, UK
4. ⁴Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, UK

Correspondence: Dr Richard H. Guy, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK. E-mail: r.h.guy@bath.ac.uk

Received 28 February 2006; Revised 15 May 2006; Accepted 22 May 2006; Published online 20 July 2006.

Abstract

The goal was to compare ibuprofen transport into and through skin in vivo in man and in vitro (across silicone membranes and freshly excised pig skin) from four marketed formulations. Ibuprofen gels were administered in vivo for 30 minutes. The stratum corneum (SC) at the application site was then tape-stripped, quantified gravimetrically, and extracted for drug analysis. Together with concomitant transepidermal water loss measurements, SC drug concentration-depth profiles were reproducibly determined and fitted mathematically to obtain a partition coefficient, a first-order rate constant related to ibuprofen diffusivity, and the total drug amount in the SC at the end of the application. All derived parameters were consistent across formulations. Ibuprofen permeation data through both silicone membrane and pig ear skin were also fitted to yield partitioning and diffusion parameters. The former revealed that ibuprofen partitioned differently from the gels into this model barrier. Across pig skin, however, better correlation with in vivo results was found. The dermatopharmacokinetic approach, using SC tape-stripping, offers a valid method to assess equivalency between topical drug formulations. In vitro experiments must be extrapolated cautiously to the clinic, especially when complex interactions between real formulations, which deliver both drug and excipients, and the skin occur.