TY  - THES
T1  - Development of a physiology based diffusion model to predict dermal absorption using experimental input parameters
A1  - Hansen,Steffi
Y1  - 2009/08/27
N2  - A physiology-based diffusion model is developed to predict drug transport across human skin. It features the "brick-and-mortar';-geometry with homogeneous lipid and corneocyte phases, accessible corneocytes and a homogeneous viable skin layer compartment. Methods are developed to determine all relevant input parameters. Partition and diffusion coefficients are measured using human abdominal skin or are estimated from experimental data, if not directly accessible. Caffeine (CAF) and flufenamic acid (FFA) serve as model drugs. The quality of the model is evaluated by comparing experimental and predicted concentration-depth-profiles. For both CAF and FFA it is found that the corneocytes have a decisive influence on stratum corneum affinity and transport.
Therefore, mechanisms of corneocyte-interactions are investigated experimentally and theoretically for the model drugs CAF, FFA, and testosterone (TST). For the non-protein binding CAF the impact of the aqueous compartment on stratum corneum partitioning is successfully modelled after introducing a bound water fraction that is non-accessible for compound dissolution. For the lipophilic, keratin binding compounds (FFA, TST) interactions are probably confined to the corneocyte surface. Binding to intracellular keratin is limited by their low aqueous solubility.
KW  - Hautresorption
KW  - Diffusionsmodell
KW  - Hornschicht
KW  - Lipide
KW  - Proteinbindung
KW  - Verteilungskoeffizient
KW  - Diffusionskoeffizient
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2009/2410
ER  -