EVALUATION OF A NOVEL DIFFUSION CELL FOR IN-VITRO TRANSDERMAL PERMEATION - EFFECTS OF INJECTION HEIGHT, VOLUME AND TEMPERATURE

The objective of this study was to evaluate the performance of a new, compact, dynamic diffusion cell for in vitro transdermal permeation. T hese so-called Kelder-cells were developed as an automated alternative to the static Franz diffusion cells. The new cells were used in combi nation with the ASPEC-system (automatic sample preparation with extrac tion columns) which was initially designed for the automation of solid -phase extractions. Three variables were tested to optimize the perfor mance of the new cell system: injection height into the inlet compartm ent, volume flowing through the receptor compartment and temperature. Experiments were performed using the tritium labelled anticholinergic [H-3]dexetimide permeating through an artificial membrane (Silastic(R) ). The injection height of the needle into the inlet compartment of th e cell should be programmed at - 34 mm to ensure complete air tightnes s, thus forcing the buffer to flow through the cell. The volume of buf fer flow through the receptor compartment is important in maintaining sink conditions: a volume of 117 mu l was chosen to replace the total content of the cell (84 mu l) every 2 min. The temperature was precise ly controlled in a thermostatic cabinet to minimize variations in expe rimental conditions. For [H-3]dexetimide, an increase in temperature o f 20 degrees C reduced the lag time by a factor of approximatley two, however the influence on the flux was negligible. The data for the Kel der-cells were comparable with static Franz diffusion cells at a pseud o-steady state, however Kelder-cells have the advantage of automatic s ampling, continuous replacement of the receptor solution, and unattend ed operation over at least 24 h. (C) 1998 Elsevier Science B.V. All ri ghts reserved.