Phase Separation of Amphiphilic Drug Amitriptyline Hydrochloride in the Presence of Additives: Role of Ethanol

In this work, the effect of ethanol (EtOH) at different weight percentages (wt %) (0, 5, 10, and 15% w/w) is accounted for in the clouding phenomena of the AMT drug with/without additives (inorganic salts and conventional and gemini surfactants). The critical micelle concentration (cmc) and degree of counterions dissociation (α) of AMT solution at 30 °C in SP buffer (pH 6.7), studied through conductometric studies, are found to be enhanced with the increase in ethanol content due to the reduction in the dielectric constant of mixed media. A dye solubilization study performed under identical physicochemical conditions exhibited supporting results. Clouding could not be observed in 20 wt % EtOH–WR mixed media at pH 6.7. The effects of additives on the CP in 15 wt % EtOH–WR at a pH of 6.95 were also studied. Furthermore, the effect of pH (range 6.7 to 7.15) on the CP in the presence of KCl at the same composition of the mixed media reduce the clouding temperature due to the deprotonation of AMT headgroups. For up to 10 wt % EtOH–WR mixed media, the effect of anionic and cationic co-ions on the CP is found to follow the order Br– > Cl– > F– and NH4+ > Li+ > Na+ > K+, respectively. When surfactants were used as additives, the hydrophobicity was found to be responsible for higher CP values and follow the order TTAB m-14, where m is the length of the spacer