ASSOCIATION AND SURFACE-PROPERTIES OF AMPHIPHILIC BENZODIAZEPINE AND BENZOTHIAZEPINE DRUGS IN AQUEOUS-SOLUTION

The mode of association in aqueous solution of three amphiphilic tranquillizing drugs, chlordiazepoxide hydrochloride, flurazepam hydrochloride, and diltiazem hydrochloride, which are benzodiazepine or benzothiazepine derivatives, has been examined by time-averaged light scattering and surface tension techniques. The association of chlordiazepoxide in water and electrolyte (concentration range 0.05-0.2 mol dm−3 NaCl) is described by a cooperative association model which assumes aggregate growth by the stepwise addition of monomers. Flurazepam and diltiazem form small micelles (aggregation number ≤ 5) by a closed association pattern in water and 0.1 mol dm−3 NaCl. Inflections in the curves of surface tension vs log concentration for all drugs are shown to be consistent with the concentrations at which enhanced light scattering is first detectable. The differences in the modes of association of these drugs are related to structural features of the drug molecules. © 1993 by Academic Press, Inc.