Ij. Bosman et al., SELECTION AND EVALUATION OF ANTICHOLINERGICS FOR TRANSDERMAL DRUG-DELIVERY, International journal of pharmaceutics, 169(1), 1998, pp. 75-82
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.