Ij. Bosman et al., STANDARDIZATION PROCEDURE FOR THE IN-VITRO SKIN PERMEATION OF ANTICHOLINERGICS, International journal of pharmaceutics, 169(1), 1998, pp. 65-73
The permeation of seven anticholinergics was studied in vitro on pig e
pidermal membranes, using static Franz diffusion cells. The donor solu
tion consisted of isotonic phosphate-buffered saline, pH 7.4 with etha
nol, propylene glycol and Azone(R). Tritium-labelled dexetimide was ad
ded as an internal standard. Ratios were calculated by dividing the pe
rcentage of permeated anticholinergic by the percentage of permeated [
H-3]dexetimide. For all anticholinergics, the use of ratios decreased
the variations which shows the usefulness of [H-3]dexetimide as an int
ernal standard to correct for variations in the skin. For all antichol
inergics, the lag times were comparable; however, the fluxes differed
by about a factor of 6 between the highest and lowest values. These di
fferences in permeation data were found not to correlate with the mole
cular weight and octanol/water partition coefficient or octanol/buffer
partition coefficient. The differences in permeation between atropine
base and atropine sulphate might be explained by differences in solub
ility and pH of the donor solution. The use of pig skin which had been
frozen and stored for 2 months at - 80 degrees C, resulted in a highe
r permeability without any lag time. Therefore only fresh skin should
be used. (C) 1998 Elsevier Science B.V. All rights reserved.