Thermodynamic solubility, solvent effect and preferential solvation analysis of rebamipide in aqueous co-solvent mixtures of propylene glycol, n-propanol, isopropanol and ethanol. (April 2020)

• Record Type: Journal Article
• Authors: Li, Wanxin; Farajtabar, Ali; Xing, Rong; Zhu, Yiting; Zhao, Hongkun; Lv, Rongguan
• Is Part Of: Journal of chemical thermodynamics. Volume 143(2020)
• Publication Date: 2020-04
• Subjects: Rebamipide -- Solubility -- Jouyban-Acree -- Preferential solvation -- Solvent effect; Thermodynamics -- Periodicals; Thermochemistry -- Periodicals; Thermodynamique -- Périodiques; Thermochimie -- Périodiques; Thermochemistry; Thermodynamics; Periodicals; 541.369
• DOI: 10.1016/j.jct.2019.106045
• Languages: English
• ISSNs: 0021-9614

Abstract

Graphical abstract: Highlights: Rebamipide solubility in four aqueous co-solvent mixtures of alcohols was determined and correlated. Solvent effect was studied in terms of solvent-solvent and solute-solvent interactions. Preferential solvation of rebamipide in four mixtures were derived through IKBIs method. Abstract: Mole fraction solubility of rebamipide (R- and S-enantiomer mixtures with a mole ratio of 50:50) in mixtures of propylene glycol (PG, 1) + water (2), n -propanol (1) + water (2), isopropanol (1) + water (2) and ethanol (1) + water (2) was reported at temperature range from (273.15 to 318.15) K. All experiments were made by the use of the isothermal saturation technique under ambient pressure of 101.2 kPa. At the same mass fraction proportions of PG, n -propanol, isopropanol or ethanol and temperature, the rebamipide solubility was highest in the PG (1) + water (2) mixture. The solubility data were correlated mathematically through the Jouyban-Acree model, attaining RAD values lower than 6.35% and RMSD values lower than 6.73 × 10 −6 . Quantitative values for local mole fraction of PG ( n -propanol, isopropanol or ethanol) and water adjacent the rebamipide were determined by means of the Inverse Kirkwood–Buff integrals method applied to the determined solubility data. The preferential solvation parameters were negative in the water-rich mixtures but positive in the co-solvent compositions from 0 to 0.20 in mole fraction of n -propanol/PG, and from 0 to 0.25 in mole fraction of ethanol/isopropanol, respectively. It was conjectured that the preference of rebamipide in water-rich mixtures could be the result from the higher basic behaviour of rebamipide molecules interacting with the proton-donor functional groups of the water. In addition, the solubility variation over the composition range was analysed by KAT-LSER model to distinguish the main factors that explained solvent effect on solubility of rebamipide in the PG ( n -propanol, isopropanol or ethanol) + water mixtures. It was found that the rebamipide solubility variation was mainly due to the change in the hydrogen bond acidity and cavity term for the ethanol (isopropanol, n -propanol) mixtures and the cavity term for the PG + water mixture.