ABSTRACT
The major issue of concern in the accuracy of in vitro skin absorption studies is the
way in which absorption of a lipophilic (hydrophobic) compound is determined.
Lipophilic chemicals that penetrate into the skin may not freely partition into the
receptor fluid beneath the skin. Therefore, skin absorption values for lipophilic
chemicals determined from receptor fluid samples may underestimate skin absorp-
tion. The problem was alluded to over 30 years ago by Franz who, in selecting
compounds for study, omitted highly lipophilic compounds to avoid results that
were “artificially limited due to insolubility in the dermal bathing solution” (1).
In the early in vivo and in vitro absorption comparisons made by Tsuruta, lower
than expected in vitro absorption values were noted for organic solvents with the
lowest water solubility (2,3). Brown and Ulsamer found that the skin permeation of
the lipophilic compound hexachlorophene increased twofold when normal saline
was replaced with 3% bovine serum albumin (BSA, in a physiological buffer) in the
diffusion cell receptor (4).