Dermatopharmacokinetic prediction of topical drug bioavailability in vivo

The overall goal of this study was to explore the potential of using stratum corneum (SC) tape-stripping, postapplication of a topical drug formulation, to derive dermatopharmacokinetic parameters describing the rate and exteW of delivery into the skin. lbuprofen was administered in 75:25 v/v propylene glycol-water to the ventral forew ms of human volunteers for periods ranging between 15 and 180 minutes. Subsequently, SC was tapestripped, quantified gravi metrically, and extracted for drug analysis. Together with concomitant transepidermal water loss measurements, SC concentration-depth profiles of the drug were reproducibly determined and fitted mathematically. The SC-vehicle partition coefficient (K) and a first-order rate constant related to ibuprofen diffusivity in the membrane (D/L-2, where L = SC thickness) were derived from data-fitting and characterized the extent and rate of drug absorption across the skin. Integration of the concentration profiles yielded the total drug amount in the SC at the end of the application period. Using K and D/L-2 obtained from the 30-minute exposure, it was possible to predict ibuprofen uptake as a function of time into the SC. Prediction and exper ment agreed satisfactorily suggesting that objective and quantitative information, with which to characterize topical drug bioavailability, can be obtained from this approach.