Calorimetry Studies of Chlorpromazine Hydrochloride in Solution

Abstract

The self-association of the tranquilizer chlorpromazine hydrochloride in aqueous solution was studied. Using isothermal titration calorimetry, the critical micelle concentration and solvent−micelle interactions were evaluated as a function of temperature, ionic strength, and pH. The enthalpy of demicellization, ΔHdemic, was directly measured from the experimental enthalpy values, which showed that the spontaneous demicellization of chlorpromazine hydrochloride is a highly endothermic process under all experimental conditions studied. The thermodynamic parameters were subsequently calculated from the temperature dependent thermograms. At 25 °C, the critical micelle concentration was determined to be 3.2 mM at pH 6.5 with a ΔHdemic of 12.5 kJ/mol, a ΔGdemic of 24.3 kJ/mol, and a TΔSdemic of −10.1 kJ/mol. Our results suggest that the enthalpy−entropy compensation theory may be applied to these micelles. In addition, using differential scanning calorimetry, a broad endothermic demicellization peak was observed in postmicelle solutions during heating scans at approximately 45 °C. Cooling scans revealed a very broad peak centered around 40 °C that corresponds to the heat of micellization.