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).