Studies on the size and stability of chlorpromazine hydrochloride nanostructures in aqueous solution

Abstract

The mean aggregate number (MAN) of the antipsychotic drug chlorpromazine hydrochloride (CPZ) nanostructure was investigated by fluorescence quenching using 9-methylanthracene (9-MA) as the quencher. The method was designed to take advantage of the intrinsic fluorescent properties of CPZ. The validity of this method was supported by the results obtained for the MAN which was determined to be approximately 37 for a solution of 10 mM CPZ in 0.1 M pH 6.5 phosphate buffer. An increase in the aggregate size with increasing drug concentration confirmed the stepwise aggregation theory of CPZ micelle formation. Differential scanning calorimetry was used to examine the effects of concentration on the thermodynamics of micellization. The enthalpy of demicellization increased with increasing CPZ concentration (5–12 mM), suggesting a greater stability of the aggregates at higher concentrations. At amphiphile concentrations higher than 12 mM, a plateau of approximately 10 kJ/mol was observed as the enthalpy of demicellization. Fluorescence lifetime results revealed a two-component system at low CPZ concentration, while data at amphiphile concentrations higher than 12 mM could not be fitted to either single or multi-component lifetime values, suggesting an increase in dispersity in these nanostructures at higher CPZ concentrations. Temperatures higher than 40°C tend to destabilize the larger micelles, and demicellization was observed after approximately 45°C. Changes in osmotic pressure in the presence of dextrose up to 0.3 M had no significant effect on the size of these micellar nanostructures.