The purpose of this study was to predict the oral absorption of glyburide. Biorelevant dissolution methods, combined with permeability measurements and computational simulations, were used to predict the oral absorption of glyburide. The objective was to establish in vitro/in vivo correlations (IVIVCs) based on the biopharmaceutics drug classification system. The solubility of the glyburide powder was measured in different media. The dissolution behavior of two commercial tablet formulations was tested in different media. Two chemical grades of sodium taurocholate: low quality (LQ) = crude and high quality (HQ) = 97% purity, and egg-lecithin: LQ = 60% and HQ = 99.1% purity were used to prepare fasted state small intestinal fluid (FaSSIF). Simulated intestinal fluid (SIF) and blank FaSSIF without lecithin and taurocholate (BL-FaSSIF) were used as controls. The dissolution tests were performed under constant pH and dynamic pH conditions. The dynamic pH range from 5.0 to 7.5 simulated the biological pH range of gastrointestinal (GI) tract in the fasted state. The drug permeability was studied using Caco-2 cell line. The predictions of the fraction dose absorbed were performed using GastroPlus™. The results of the simulations were compared with actual clinical data taken from a bioequivalence study. The solubility of glyburide was highest in LQ-FaSSIF. The two tablet formulations had significantly different dissolution behaviors in LQ-FaSSIF. The in vitro data was used as the input function into a simulation software. The dynamic LQ-FaSSIF dissolution data achieved the best prediction of the average AUC and Cmax of the clinically observed data. The present study shows that BCS based parameters combined with software simulations can be used to establish an IVIVC for glyburide. In vitro/in silico tools can potentially be used as surrogate for bioequivalence studies.