Investigation of Micellar and Phase Separation Phenomenon of the Amphiphilic Drug Amitriptyline Hydrochloride with Cationic Hydrotropes

Micellization and phase separation of the amphiphilic drug amitriptyline hydrochloride (AMT) in the absence and presence of cationic hydrotropes (aniline hydrochloride, para-toluidine hydrochloride, and ortho-toluidine hydrochloride) have been investigated in the present study. The experimental critical micelle concentration (cmc) values are lower than cmc ^id values (cmc ^id is the cmc value at ideal mixing state), indicating attractive interactions between the two components (drug and hydrotrope) in mixed micelles. The bulk behaviors were investigated using the different theoretical models of Clint, Rubingh, Motomura, and Rodenas for comparison of the results of different binary combinations of the drug and hydrotropes. Synergistic interactions were confirmed in all binary combinations at all temperatures, which increase with increasing concentration of hydrotropes. Activity coefficients (f ₁ and f ₂) were found to be consistently less than unity indicating nonideality in the systems. At a fixed drug concentration (50 mmol·dm^?3) and pH (6.7), the hydrotropes showed a continuous increase in the cloud point. Thermodynamic parameters were also evaluated and discussed in detail.