STANDARDIZATION PROCEDURE FOR THE IN-VITRO SKIN PERMEATION OF ANTICHOLINERGICS

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.