LAUSR

(Z)-N-Benzyl-2-{2,4-dioxo-5-(4-prop-2-yl-1-yloxyl)benzylidene)thiazolin-3-yl)}acetamide (SE415) is a novel aldose reductase inhibitor used in the management of diabetes mellitus (DM) and associated complications. Herein, the drug was solubilized (mole fraction solubility) in a “PEG 400 (polyethylene glycol 400) + water” mixture of various ratios at 298.15 K. We reported the preferential solvation of SE415 by PEG 400 using Kirkwood–Buff integrals, the thermodynamic functional parameter, in vitro dissolution, and GastroPlus-based predictions for in vivo performance. The result of Hansen solubility parameter analysis suggested PEG 400 as a suitable solvent for SE415 solubilization at 298.0 K, followed by prediction of several physicochemical properties. In the preferential solvation study, the molar volume, Hildebrand solubility parameters, and the molecular radius of SE415 were estimated as 258.4 cm3·mol–1, 27.62 MPa1/2, and 0.468 nm, respectively, using Fedors’ method. The inverse Kirkwood-Buff integrals indicated that the preferential solvation of SE415 by PEG 400 occurred in all studied ratios of the (PEG 400 + water) mixtures. The maximum value (δx1,3 = 1.21 × 10–2) of the preferential solvation of SE415 by PEG 400 was achieved at x1 = 0.15. Then, using GastroPlus software, the maximum dissolution, improved in vivo oral absorption, and high regional compartmental absorption (total 99.0%) of SE415 in humans were predicted. Finally, the solubility data were correlated/predicted using various cosolvency models with satisfactory results. Thus, the binary cosolvent system can be a promising approach for enhanced oral absorption in controlling DM and associated complications in humans.