A Calorimetric Study of the Influence of Temperature on the Self-Association of Amphiphilic Antidepressant Drugs in Aqueous Solution

Relative apparent molar enthalpies have been determined as a function of concentration (0.0001 to 0.2 mol kg(-1)) by heat conduction calorimetry for aqueous solutions of the structurally related antidepressant drugs imipramine and clomipramine in water over the temperature range 288 to 308 K. Critical concentrations determined from inflections in these plots for both drugs had minimum values at 298 K. The concentration dependence of the relative apparent molar enthalpy could be quantitatively described using a mass action model of association based on the Guggenheim equations for the activity coefficients of mixed electrolytes. Derived values of the monomer-counterion interaction coefficient for imipramine became increasingly negative with an increase in temperature over the temperature range 293 to 303 K, indicative of an increasing degree of premicellar association. In contrast, negative monomer-counterion interaction coefficients were obtained for clomipramine at only 303 and 308 K, suggesting an absence of premicellar association at lower temperatures. Values derived for the molar enthalpy of micellization of both drugs from the mass action model indicate an increasingly exothermic process with increase in temperature; positive values at 288 and 293 K arise from hydrophobic interactions while the negative values at higher temperatures suggest the importance of London dispersion interactions as the major driving force for aggregation. Copyright 2000 Academic Press.