Effect of Organic Additives on the Phase Separation Phenomenon of Amphiphilic Drug Solutions

Abstract The effect of various organic additives, viz. sugars, ureas, alcohols, hydrotropes and bile salts on the clouding (phase separation) phenomenon of the amphiphilic antidepressant drug amitriptyline hydrochloride was investigated in the present study. All sugars lowered the cloud point (CP) due to their water structure‐making property. Urea and alkylureas were found to lower the CP. In contrast, thioureas increased the CP slightly, but the presence of methyl group(s) had a similar effect in alkylureas. Short chain alcohols affected the CP insignificantly while higher ones decreased it, and medium chain alcohols showed peak behavior. Addition of hydrotropes and bile salts increased the CP at lower concentrations, while a decrease was observed at higher concentrations (like the medium chain alcohols). In addition, thermodynamic parameters were also evaluated but only for those additives which formed mixed micelles with the drug.