COMPLEX AGGREGATION PATTERNS FOR THE SELF-ASSOCIATION OF PHENOTHIAZINE DRUGS IN AQUEOUS-SOLUTION

Time-average light scattering and ultrasound velocity measurements on aqueous solutions of the amphiphilic phenothiazine drugs, chlorpromazine hydrochloride, promethazine hydrochloride, and promazine hydrochloride at 30°C showed discontinuities at two critical concentrations. The first critical concentration (c1) corresponded to the literature values of the critical micelle concentration (CMC); the second (c2) occurred at concentrations in the region 0.20 to 0.27 mol kg-1. Increase of temperature over the range 5 to 25°C had no significant effect on either c1 or c2 for the chlorpromazine hydrochloride/water system. An appreciable increase of c1 was observed between 25 and 45°C which was accompanied by a decrease of c2. An increase of degree of micellar ionization with temperature increase from 5 to 45°C was noted, with values ranging between 0.10 and 0.29. No significant temperature dependence of the aggregation number could be discerned. Three inflection points were observed in plots of light scattering intensity and ultrasound velocity against molality for solutions of chlorpromazine hydrochloride in 0.025 mol dm-3 sodium chloride, whilst two inflection points were noted in the presence of 0.100 mol dm-3 sodium chloride. The significance of the critical concentrations is discussed in terms of the mode of association of these drugs. © 1991.