title: A strategy for in-silico prediction of skin absorption in man.
abstract: For some time, in-silico models to address substance transport into and through the skin are gaining more and more importance in different fields of science and industry. In particular, the mathematical prediction of in-vivo skin absorption is of great interest to overcome ethical and economical issues. The presented work outlines a strategy to address this problem and in particular, investigates in-vitro and in-vivo skin penetration experiments of the model compound flufenamic acid solved in an ointment by means of a mathematical model. Experimental stratum corneum concentration-depth profiles (SC-CDP) for various time intervals using two different in-vitro systems (Franz diffusion cell, Saarbruecken penetration model) were examined and simulated with the help of a highly optimized three compartment numerical diffusion model and compared to the findings of SC-CDPs of the in-vivo scenario. Fitted model input parameters (diffusion coefficient and partition coefficient with respect to the stratum corneum) for the in-vitro infinite dose case could be used to predict the in-use conditions in-vitro. Despite apparent differences in calculated partition coefficients between in-vivo and in-vitro studies, prediction of in-vivo scenarios from input parameters calculated from the in-vitro case yielded reasonable results.
authors.affiliation: Biopharmaceutics and Pharmaceutical Technology, Saarland University, D-66123 Saarbruecken, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Selzer
authors.affiliation: Scientific Consilience, Saarland University, D-66123 Saarbruecken, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Neumann
authors.affiliation: Biopharmaceutics and Pharmaceutical Technology, Saarland University, D-66123 Saarbruecken, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Neumann
authors.affiliation: Dept. of Plastic and Hand Surgery, Caritaskrankenhaus, D-66822 Lebach, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Kostka
authors.affiliation: Biopharmaceutics and Pharmaceutical Technology, Saarland University, D-66123 Saarbruecken, Germany; Dept. of Drug Delivery (DDEL), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, D-66123 Saarbruecken, Germany.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
authors.affiliation: Biopharmaceutics and Pharmaceutical Technology, Saarland University, D-66123 Saarbruecken, Germany. Electronic address: ufs@mx.uni-saarland.de.
authors.forename: Ulrich F
authors.initials: UF
authors.lastname: Schaefer
mesh_terms: D000328:Adult; D003198:Computer Simulation; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D005260:Female; D005439:Flufenamic Acid / Q000008:administration & dosage* / Q000378:metabolism*; D006801:Humans; D008297:Male; D009924:Organ Culture Techniques; D011237:Predictive Value of Tests; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology*; D055815:Young Adult
chemical_list: D005439:Flufenamic Acid
keywords: Diffusion model; In-vitro studies; In-vivo studies; Semisolid drug preparations; Skin concentration–depth profiles