Aggregation of antiacetylcholine drugs in aqueous solution: monomer concentrations in non-micellar drug systems.

The self-association of the antiacetylcholine drugs, propantheline bromide, methantheline bromide and methixene hydrochloride in aqueous solution, has been examined by surface tension, light scattering and conductimetric methods. Surface tension graphs were similar to those of conventional surfactants, showing apparent critical micelle concentrations (cmc) at distinct inflection points. Surface tension measurements in the presence of increasing amounts of electrolyte indicated a decrease in the apparent cmc with increase in electrolyte concentration for propantheline bromide. Light scattering curves for propantheline bromide in electrolyte solution showed no significant discontinuity attributable to a cmc. A mode of self association involving aggregate growth by the stepwise addition of monomers was assumed and equilibrium constants for the initial stages of the association were evaluated. An increase in the magnitude of the stepwise association constants with increase in electrolyte concentration was noted. Integration of the light scattering data according to 1n x = oo [(M/Mapp) - 1] dln c (where M and M app are the monomer and apparent aggregate weights respectively and x is the weight fraction of monomers) showed an asymptotic increase in monomer concentration towards a limiting concentration, as the solution concentration, c was increased. Limiting monomer concentrations determined by this method were in reasonable agreement with the apparent cmcs from surface tension studies. It was not possible to detect a cmc for methantheline or propantheline bromide from conductivity measurements.