pH-dependent phase transition of chlorpromazine micellar solutions in the physiological range.

The effects of pH and drug concentration on aggregation properties of chlorpromazine-HCl (CPZ) are examined. The critical micelle concentration (cmc) changes from 0.2 mM at pH 7.3 to 2 mM at pH 5.6 as estimated from the stearic acid spin label solubility measurements. For concentrations above the cmc CPZ micelles undergo a concentration-, temperature- and pH-dependent transition leading to phase separation. This phase transition is followed by a sudden increase of light scattering. The phase diagram pH vs. concentration is obtained by observation of the cloud point for concentrations ranging from 0.01 to 10 mM. The intramicellar environment is probed at pH ranging from 5.5 to 8.0 using a stearic acid spin label. The intramicellar compactness increases smoothly with increasing pH suggesting the weakening of polar heads repulsion due to charge decrease. The reported results indicate that pH effects are relevant and should be properly taken into account in the performance and interpretation of experiments with CPZ.