Ij. Bosman et al., EVALUATION OF A NOVEL DIFFUSION CELL FOR IN-VITRO TRANSDERMAL PERMEATION - EFFECTS OF INJECTION HEIGHT, VOLUME AND TEMPERATURE, Journal of pharmaceutical and biomedical analysis, 17(3), 1998, pp. 493-499
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.