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, ∆Hdemic, 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 ∆Hdemic of 12.5 kJ/mol, a ∆Gdemic of 24.3 kJ/mol, and a T∆Sdemic 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.

Thermodynamic Characterization of Temperature-Induced Micellization and Demicellization of Detergents Studied by Differential Scanning Calorimetry

“…Another recent publication reported results from temperature-induced demicellization of chlorpromazine hydrochloride. However, this aggregation process seems to be significantly different from the micellar aggregation of surfactants with alkyl chains …”

What can isothermal titration microcalorimetry experiments tell us about the self‐organization of surfactants into micelles?

“…However, in ITC measurements, the temperature of the experiment remains unchanged while the surfactant concentration is progressively increased in the measurement cell. However, other research works (Saito et al, 2000) reported very slightly different values of DH mic for chlorpromazine hydrochloride (ionic surfactant) detemined from DSC and ITC experiments. The amplitude of the discrepancy might thus depend on the nature of the surfactant.…”

Impact of Chlorpromazine Self-Association on Its Apparent Binding Constants With Cyclodextrins: Effect of SBE7-β-CD on the Disposition of Chlorpromazine in the Rat

“…The binding constant for chlorpromazine with SBE 7 -b-CD was also determined using fluorescence spectroscopy, although measurement of the binding constant was complicated by the fact that chlorpromazine exhibits self-association behaviour. [6][7][8][9][10][11] Several publications, using a range of techniques including isothermal titration calorimetry, 10 octanol-water partitioning, 8 surface tension measurements, 7 stearic acid spin label solubility measurements, 9 fluorescence 6 and UV-visible spectrophotometry 11 have reported CMCs for chlorpromazine covering a wide range (Tab. 1).…”