Chlorpromazine Hydrochloride Micellization and the Thermodynamics of Aggregation in Aqueous Solution.
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The mean aggregate number (MAN) of the antipsychotic drug chlorpromazine hydro-chloride (CPZ) was investigated by fluorescence quenching. Using the intrinsic fluorescent properties of CPZ micelles and the quenching effect of 9-methylanthracene (9-MA), the MAN was determined to be ca. 30. A pronounced increase in aggregate size with in-creasing drug concentration (0.005-0.020 M CPZ) further confirmed the stepwise aggregation theory of CPZ. Increasing temperatures (>313 K) hindered the stability of larger micelles. Increasing electrolyte concentrations (0.0-0.4 M NaCl) resulted in increasing aggregate size, while higher osmotic pressures (0.0-0.3 M dextrose) had no significant effect on the micelle size. The enthalpy of micellization and demicellization for CPZ in a buffered solution were measured by differential scanning calorimetry. Post-micelle solutions of CPZ in buffer showed an abrupt, endothermic peak during upscans at ca. 318 E K. The peak was assigned as that of demicellization. Down scans revealed a broad peak due to the heat of micellization. Integration of peaks revealed changes in enthalpy values of -9 and 9 kJ per mole for micellization and demicellization respectively.