Preferential solvation study of (Z)-N-benzyl-2-{5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (3) in {NMP + Water } co-solvent mixture and GastroPlus software based in vitro simulation

Abstract

(Z)-N-benzyl-2-{5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (3) (SE11) is a newly synthesized benzylidine thiazolidinedione to inhibit aldose reductase (AR) to control Diabetes Mellitus (DM) and related complications. This reported compound exhibits poor water solubility and based on Hansen solubility parameter (HSP) considerations NMP (N-methyl-2-pyrrolidone) is expected to be a suitable co-solvent. SE11 was soluble in various ratios of (NMP + water) mixture at 298.15 K. Moreover, preferential-solvation (PS) of SE11 by the mixed components was investigated (thermodynamic functional parameters and Kirkwood-Buff integrals) followed by in-vitro dissolution, and simulation (GastroPlus) of dissolution data for the best fit of Weibull model. Hansen solubility parameters (HSP) analysis suggested NMP as the most relevant solvent for SE11 solubility at 298 K and predicted physicochemical properties. In PS, the molar-volume (214.0 cm3·mol−1), Hildebrand solubility parameter (31.11 MPa1/2), and molecular-radius (0.44 nm) of SE11 were calculated. The inverse Kirkwood-Buff integral computational analysis showed that the PS of SE11 through NMP was found in all explored ratios. The highest value (δx1,3 = 0.67 × 10–2) of PS was obtained at x1 = 0.60–0.65 in NMP. Finally, the GastroPlus software simulated in vitro dissolution profile and the impact of shape factor on release behaviour followed by computational assessment. Hence, the explored binary mixture can be used as a suitable approach to treat systemic DM.