Calorimetric study of the influence of electrolyte on the micellization of phenothiazine drugs in aqueous solution

Apparent molar enthalpies have been determined as a function of concentration by heat conduction calorimetry for aqueous solutions of the phenothiazine drugs chlorpromazine hydrochloride, promethazine hydrochloride, and promazine hydrochloride in the presence of added electrolyte (0.025-0.10 mol dm(-3) NaCl). The concentration dependence of the apparent molar enthalpy could be quantitatively described using a mass action model of association based on the Guggenheim equations for the activity coefficients for mixed electrolytes. Derived values of the monomer-counterion interaction coefficient became increasingly negative with increase of salt concentration, suggesting that electrolyte addition promoted association at concentrations below the critical micelle concentration (cmc). Calculations of the fraction of each drug in the form of micelles as a function of concentration further confirmed the tendency for premicellar association. Significant differences in properties were observed between promethazine and the other two drugs. The micellization of this drug became increasingly exothermic with increase of electrolyte concentration, whereas the micellization of both chlorpromazine and promazine became increasingly endothermic. Moreover, the premicellar association of promethazine was more pronounced, the predicted fraction of drug in micellar form at the cmc increasing from 2.6% in water to 65% in 0.1 mol dm(-3) NaCl.