Reduction of the Bitter Taste Intensity of Propantheline Bromide by Cyclodextrins As Predicted by Surface Tension Measurements

Abstract

The surface tension and the bitter taste intensity of aqueous solutions of propantheline bromide alone and of complexes with R-, -, and γ-cyclodextrin have been determined, and a unique correlation between these quantities has been found to hold regardless of the kind and concentration of the cyclodextrin. The surface tension of an aqueous solution of propantheline bromide increases on addition of one of the cyclodextrins, and the effectiveness in surface tension enhancement decreases in the order -, γ-, R-cyclodextrin. Analysis of these surface tension data yields the equilibrium constants of 1:1, 1:2, and 2:1 complexations of propantheline bromide and R-, -, γ-cyclodextrin. These binding constants are in excellent agreement with those estimated by spectrophotometry. As well as the equimolar complex, -cyclodextrin forms the 1:2 complex, and γ-cyclodextrin forms the 2:1 complex. The dimer of propantheline bromide can be incorporated into γ-cyclodextrin. Although the dimer is not included into R-and -cyclodextrins, the extent of complexation is decreased by the dimerization. The bitter taste of propantheline bromide is suppressed by adding one of the cyclodextrins. The order of this suppression agrees with that of surface tension enhancement. From the relationship between the surface tension and the bitter taste intensity of aqueous solutions of propantheline bromide and the observed value of surface tension for an aqueous solution of propantheline bromide and one of the cyclodextrins, we can predict the bitter taste intensity of the mixed solution. Molecular models of some complexes of propantheline bromide and cyclodextrins have been proposed on the basis of size and shape of these molecules and the affinity of each group of propantheline bromide to the cyclodextrin cavity.

Masking Mechanisms of Bitter Taste of Drugs Studied with Ion Selective Electrodes

“…One and two b-CyD molecules form 1 : 1 and 2 : 1 complexes with a PB molecule, whereas g-CyD forms 1 : 1 and 1 : 2 complexes with PB. 17) However, because these 1 : 2 and 2 : 1 binding constants are 1156 Vol. 54, No.…”

“…This deviation will be ascribed to dimerization of PB. 17,25) In this work we neglected the effect of dimerization of PB on the electromotive force, because it was small. Therefore, we can modify Eq.…”

“…14) As well known, a concentrated solution of sucrose masks the bitter taste of drugs by its intense sweetness. Cyclodextrins (CyDs) can reduce the bitter taste of drugs by complex formation 4,[14][15][16][17][18] : The complexed drug is not bitter, whereas the uncomplexed drug is bitter. This masking mechanism was established quantitatively.…”

“…This masking mechanism was established quantitatively. 4,17,18) Lipoprotein that is composed of phosphatidic acid, b-lactoglobulin, bovine serum albumin, and other substances is a good masking agent. [19][20][21] Some polysaccharides, synthetic polymer, and jellies can mask the bitter taste of drugs.…”

“…As already reported, suppression of the bitter taste of PB by native CyDs (a-, b-, and g-CyDs) can be predicted from the observed surface tensions of mixed solutions of PB and one of the CyDs. 17) Furthermore, masking of the bitter taste of OB by the native CyDs and several modified CyDs has been investigated with the OB ion selective electrode. 4) The ion selective electrode method will be applicable to more masking agents than the surface tension method, because the latter method is inapplicable to surface active masking agents.…”