Study of the additive effect on the cloud point of nortriptyline hydrochloride solutions

The cloud point (CP) phenomenon has been studied in amphiphilic drug nortriptyline hydrochloride solutions with or without additives. The drug solutions were prepared in 10 mM sodium phosphate buffer. An increase in pH decreases the solution CP in the absence as well as the presence of additives (urea and TBuAB) due to deprotonation of the drug molecules. At constant pH (7.07), addition of simple salts (NaF, NaCl, NaBr) increases the CP by increasing the micelle hydration. Addition of Br salts (LiBr, NaBr, KBr) also increases the CP. The behavior is explained on the basis of the cation hydrated radius. Quaternary ammonium bromides, due to adsorption/mixed-micelle formation, also increase the CP, the order being: Bu<Pr<Et<Me. The urea family additives influence CP in both ways depending on whether they contain the >C = O or >C = S moiety. The former interacts with the micelles and decreases CP while the latter (due to its electropositive character) may not interact and hence increases CP.