Abstract
Mathematical modeling of skin transport is considered a valuable alternative of in-vitro and in-vivo investigations especially considering ethical and economical questions. Mechanistic diffusion models describe skin transport by solving Fick’s 2nd law of diffusion in time and space; however models relying entirely on a consistent experimental data set are missing. For a two-dimensional model membrane consisting of a biphasic stratum corneum (SC) and a homogeneous epidermal/dermal compartment (DSL) methods are presented to determine all relevant input parameters.
The data were generated for flufenamic acid (
M
W 281.24
g/mol;
log
K
Oct
/
H
2
O
4.8; p
K
a 3.9) and caffeine (
M
W 194.2
g/mol;
log
K
Oct
/
H
2
O
−0.083; p
K
a 1.39) using female abdominal skin.
K
lip/don (lipid-donor partition coefficient) was determined in equilibration experiments with human SC lipids.
K
cor/lip (corneocyte-lipid) and
K
DSL/lip (DSL-lipid) were derived from easily available experimental data, i.e.
K
SC/don (SC-donor),
K
lip/don and
K
SC/DSL (SC-DSL) considering realistic volume fractions of the lipid and corneocyte phases. Lipid and DSL diffusion coefficients
D
lip and
D
DSL were calculated based on steady state flux. The corneocyte diffusion coefficient
D
cor is not accessible experimentally and needs to be estimated by simulation.
Based on these results time-dependent stratum corneum concentration-depth profiles were simulated and compared to experimental profiles in an accompanying study.