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, post-application of a topical drug formulation, to derive dermatopharmacokinetic parameters describing the rate and extent of delivery into the skin. Ibuprofen was administered in 75:25 v/v propylene glycol-water to the ventral forearms of human volunteers for periods ranging between 15 and 180 minutes. Subsequently, SC was tape-stripped, quantified gravimetrically, 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/L2, 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/L2 obtained from the 30-minute exposure, it was possible to predict ibuprofen uptake as a function of time into the SC. Prediction and experiment agreed satisfactorily suggesting that objective and quantitative information, with which to characterize topical drug bioavailability, can be obtained from this approach.
Herkenne
Christophe
C
School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.
Naik
Aarti
A
Kalia
Yogeshvar N
YN
Hadgraft
Jonathan
J
Guy
Richard H
RH
D000042:Absorption; D000287:Administration, Topical; D000328:Adult; D001682:Biological Availability; D004817:Epidermis / Q000378:metabolism; D005260:Female; D005542:Forearm; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D010599:Pharmacokinetics; D011237:Predictive Value of Tests; D012867:Skin / Q000378:metabolism*; D012996:Solutions; D053832:Surgical Tape
D012996:Solutions; D007052:Ibuprofen