SELECTION AND EVALUATION OF ANTICHOLINERGICS FOR TRANSDERMAL DRUG-DELIVERY

The receptor affinities of 18 anticholinergics, expressed as dissociat ion constants, were determined in order to select the most active comp ounds. Six drugs showed high affinities towards the muscarinic recepto r (K-d < 30 nM), and these compounds were selected as possible candida tes for transdermal drug delivery because they can theoretically provi de therapeutic plasma concentrations by dermal application on a limite d area. From the six selected anticholinergics (atropine sulphate mono hydrate. benztropine mesylate, dexetimide hydrochloride, oxyphencyclim ine hydrochloride, scopolamine hydrobromide trihydrate; tropicamide), the physicochemical characteristics are described, together with atrop ine base. These characteristics may be useful to explain possible diff erences in permeation experiments. The chemical structures, molecular weights, and pK(a) values were available from the literature. The part ition coefficients, and the solubility, pH and stability in the dosing and receptor solutions were experimentally determined. (C) 1998 Elsev ier Science B.V. All rights reserved.