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 concen tration by heat conduction calorimetry for aqueous solutions of the ph enothiazine drugs chlorpromazine hydrochloride, promethazine hydrochlo ride, and promazine hydrochloride in the presence of added electrolyte (0.025-0.10 mol dm(-3) NaCl). The concentration dependence of the app arent molar enthalpy could be quantitatively described using a mass ac tion model of association based on the Guggenheim equations for the ac tivity coefficients for mixed electrolytes. Derived values of the mono mer-counterion interaction coefficient became increasingly negative wi th increase of salt concentration, suggesting that electrolyte additio n promoted association at concentrations below the critical micelle co ncentration (cmc). Calculations of the fraction of each drug in the fo rm of micelles as a function of concentration further confirmed the te ndency for premicellar association. Significant differences in propert ies were observed between promethazine and the other two drugs. The mi cellization of this drug became increasingly exothermic with increase of electrolyte concentration, whereas the micellization of both chlorp romazine and promazine became increasingly endothermic. Moreover, the premicellar association of promethazine was more pronounced, the predi cted fraction of drug in micellar form at the cmc increasing from 2.6% in water to 65% in 0.1 mol dm(-3) NaCl.