Self-Assembly and Thermodynamic Parameters of Amitriptyline Hydrochloride in Polar Organic Solvent-Water Mixed Media Jackson Gurung and Ajmal Koya Pulikkal* Department of Chemistry, National Institute of Technology Mizoram, Chaltlang, Aizawl 796012, India * S Supporting Information ABSTRACT: Organic solvent-water mixed media find applications in industrial, chemical, and pharmaceutical areas. This work discusses the micellization and related parameters such as degree of counterion dissociation (α), change in Gibbs energy of micellization (ΔG m 0 ) of an amphiphilic drug amitriptyline hydrochloride (AMT), and Gordon parameter (G p ) in three polar organic solvents, viz., ethanol (EtOH), ethylene glycol (EG), and glycerol (GL)-water mixed media, with a special focus on the effects of a wide range of polarity changes. A decrease in conductivity of the solution and an enhancement of critical micelle concentration (cmc) of AMT are found with the increase in weight percentage (wt %) of the organic solvents in their mixed media at a pH of 6.7 and a temperature of 303.15 K. The cmc and absorbance values evaluated from conductivity and dye solubilization measurements, respectively, reveal that the GL-water mixed media behave as a better system for AMT compared to the EG-water and EtOH-water mixed media. The calculated values for ΔG m 0 in all the compositions of the mixed media were negative, which increase with the increase in wt % of the studied organic solvents. 1. INTRODUCTION The surface-active nature of amphiphiles plays a vibrant role in several phenomena owing to the hydrophobic and hydrophilic portion in their molecular structure. These are the versatile molecules being used in diverse fields such as detergents, foams, pharmaceuticals, paints, inks, biological, petroleum industry, and medical technologies. 1-4 They have the tendency to segregate into an interface and to subsequently reduce the surface tension of aqueous media. The process of aggregation is mostly driven by the hydrophobic effects, resulting in the formation of micelles above a certain minimum concentration termed as critical micelle concentration (cmc). Micelles, which are dynamic in nature, have colloidal dimension and are thermodynamically stable because of subtle balance between hydrophobic and electrostatic interactions. The self-aggregation and morphology of micelles can be altered by changing the molecular structure of amphiphiles and solution conditions such as temperature, pH, and concen- tration or by inclusion of additives. 3,5,6 As solvophobic and solvophilic interactions can stimulate the micellar/interfacial properties, the effect can be modified by changing the bulk properties of the solvent. Many works have been reported in the literature about the effect of organic solvent-water mixed media on the micellization of various types of surfactants. 7-22 Organic solvents such as glycerol (GL), ethylene glycol (EG), ethanol (EtOH), and so forth have been frequently used in many of these studies. 7-9,11,15,16,21 The choice of these solvents has been justified by their relatively higher polarity, good miscibility with pure water, hydrogen bonding competence, and so forth. Amitriptyline hydrochloride (AMT) is an amphiphilic antidepressant drug, which possesses a hydrophobic tricyclic ring and a short hydrocarbon chain consisting of tertiary amines. The interaction of drugs with the biomembrane (which can be considered as a complex form of amphiphilic bi- layers) exerts anesthetic, analgesic, tranquillizing, antibiotic, and antidepressant activities of the drugs. 23-25 AMT is a biologically significant compound, which is usually used to treat mental or mood issues including depression. The solvents such as GL, EG, EtOH, and so forth find applications in detergency, pharmaceutical, and cosmetic industries. 26-29 Therefore, knowledge about the micellization and thermody- namic parameters of amphiphilic drugs in mixed media is important from both fundamental and application point of views. As far as amphiphilic drugs are concerned, plenty of works have been devoted to understand the effects of various types of additives on their properties and interaction between the surface-active agents and amphiphilic drug in an aqueous medium. 25,30-37 To the best of our knowledge, however, such studies in organic solvent-water mixed media are very limited except our own previous works. 38,39 Herein, we report the micellization and related thermodynamic parameters of AMT in GL-water, EG-water, and EtOH-water mixed media. The molecular structure of the drug and the organic solvents used in the study are given in Scheme 1. The compositions of the studied solvents in the mixed media were varied between 0 and Received: June 11, 2019 Accepted: August 27, 2019 Article pubs.acs.org/jced Cite This: J. Chem. Eng. Data XXXX, XXX, XXX-XXX © XXXX American Chemical Society A DOI: 10.1021/acs.jced.9b00542 J. Chem. Eng. 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