Standardization procedure for the in vitro skin permeation of anticholinergics

• Published in: International journal of pharmaceutics 1998-06, Vol.169 (1), p.65-73
• Main Authors: Bosman, Ingrid J., Ensing, Kees, de Zeeuw, Rokus A.
• Format: Article
• Language: English
• Subjects: [ 3H]Dexetimide; Anticholinergics; Biological and medical sciences; General pharmacology; In vitro permeation; Internal standard; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Transdermal delivery
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(98)00106-9

The permeation of seven anticholinergics was studied in vitro on pig epidermal membranes, using static Franz diffusion cells. The donor solution consisted of isotonic phosphate-buffered saline, pH 7.4 with ethanol, propylene glycol and Azone®. Tritium-labelled dexetimide was added as an internal standard. Ratios were calculated by dividing the percentage of permeated anticholinergic by the percentage of permeated [ 3H]dexetimide. For all anticholinergics, the use of ratios decreased the variations which shows the usefulness of [ 3H]dexetimide as an internal standard to correct for variations in the skin. For all anticholinergics, the lag times were comparable; however, the fluxes differed by about a factor of 6 between the highest and lowest values. These differences in permeation data were found not to correlate with the molecular 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 solubility and pH of the donor solution. The use of pig skin which had been frozen and stored for 2 months at −80°C, resulted in a higher permeability without any lag time. Therefore only fresh skin should be used.