Finite and infinite dosing: difficulties in measurements, evaluations and predictions.

Due to the increased demand for reliable data regarding penetration into and permeation across human skin, assessment of the absorption of xenobiotics has been gaining in importance steadily. In vitro experiments allow for determining these data faster and more easily than in vivo experiments. However, the experiments described in literature and the subsequent evaluation procedures differ considerably. Here we will give an overview on typical finite and infinite dose experiments performed in fundamental research and on the evaluation of the data. We will point out possible difficulties that may arise and give a short overview on attempts at predicting skin absorption in vitro and in vivo.

Influence of the application area on finite dose permeation in relation to drug type applied.

For finite dose skin absorption experiments, a homogeneous donor distribution over the skin surface is usually assumed. However, the influence of the surface distribution on skin absorption is still unknown. The aim of this study was to evaluate the influence of the application area on the permeation of drugs during finite dose skin absorption experiments in static Franz diffusion cells. Permeation experiments with stained aqueous drug formulations were conducted, and the application area was determined by a suitable, objective, automated computational approach. The permeation of caffeine is strongly dependent on the application area. The variability between single experiments decreased when including the application area. For the lipophilic flufenamic acid, this was not the case. The variability highly increased after inclusion of the application area. Thus, a correction of the area is misleading. In summary, depending on the drug's physicochemical characteristics, the application area may influence skin absorption.

In vitro human skin segmentation and drug concentration-skin depth profiles.

Highly optimized methods for skin segmentation are provided using tape stripping in combination with infrared absorption measurements for stratum corneum (SC) and cryosectioning for deeper skin layers. Furthermore, an example is calculated for demonstration of the respective procedures.