Clouding behavior of antidepressant drug–additive system in ethylene glycol/glycerol–water mixed media and their thermodynamic parameters at cloud point

Abstract

The influence of ethylene glycol (EG)/glycerol(GL)–water mixed media on clouding action of an amphiphilic drug, amitriptyline hydrochloride (AMT) at pH 6.7 with inorganic salts (KF, KCl, KBr, LiCl, NaCl, and NH₄Cl) in selected compositions of EG–WR and GL–WR mixed media (0%, 5%, 10%, 15%, and 20% of EG/GL, w/w) and their thermodynamic parameters at cloud point (CP) were studied. Experimentally determined critical micellization concentration (cmc) values (up to 25% w/w with an increment of 5% w/w) by conductivity measurements and results of dye solubilization by a UV-visible spectroscopic technique show that the micellization of AMT drug molecules is affected by an indirect, solvent-mediated mechanism with increasing weight% of EG and GL in their binary mixture due to a diminution in the dielectric constant of mixed media. A rise in CP of the AMT solution was observed with an increase in weight% of organic solvent in the mixed media in the absence and presence of the salts. The results demonstrated that CP behavior depends on the interaction of solvent with the drug micelles as well as with the hydrated/solvated radii of these ions. F⁻ and Br⁻ co-ions show a prominent effect in higher weight% of the binary mixtures. Δ_sG⁰ values were found to be positive for all the additives whereas Δ_sH⁰ and TΔ_sS⁰ were positive except in presence of KF in 20% EG–WR mixed media. The results are discussed by considering the solvent effect on electrostatic interaction and based on hydrated/solvated sizes of the ions.