An improved in vitro method for measuring skin permeability that controls excess hydration of skin using modified Franz diffusion cells.

When liquid donors/receivers are used for in vitro skin permeation studies, excess hydration can change skin properties compared to in vivo conditions. A novel in vitro method of determining the permeability of drugs through skin was developed that avoids exposing the membrane to dilute donor/receiver solutions. The drug is dissolved in an unstirred donor gel, and diffuses through a membrane into an unstirred gel receiver that can potentially be adjusted to mimic physiological conditions. Pulsatile microdialysis (PMD) was used to sample local concentrations in the receiver medium, and a model was developed to allow the determination of permeability. For Doxepin HCl, permeabilities through artificial membranes and human cadaver skin were determined using the new and previously reported methods. For artificial membranes that minimally hydrate, the new method gave consistent but slightly lower permeability values. For human cadaver skin, the permeability determined using the new method was 1/6 that of the fully hydrated skin. Limitations of the model, their relations to experimental design and data analysis were evaluated. It was concluded that this method can be applied to characterize membrane permeabilities using experiments that may avoid membrane breakdown and more closely mimic physiological conditions.