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The aim of this study was to investigate the physicochemical properties of glimepiride in SDs with PEG 20000. The phase solubility behavior of glimepiride in presence of various concentrations of PEG 20000 in pH 7.4 buffer was obtained at 37oC. The solubility of glimepiride increased with increasing amount of PEG 20000 in pH 7.4 buffer. Gibbs free energy (ΔGotr) values were all negative, indicating the spontaneous nature of glimepiride solubilization and ΔGotr decreased with increase in the PEG 20000 concentration, demonstrating that the reaction conditions became more favorable as the concentration of PEG 20000 increased. The SDs of glimepiride with PEG 20000 were prepared at 1:1, 1:3 and 1:5 (glimepiride: PEG 20000) ratio by melting method. Evaluation of the properties of the SDs was performed by using dissolution, Fourier-transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) studies. The SDs of glimepiride with PEG 20000 exhibited enhanced dissolution rate of glimepiride, and the rate increased with increasing concentration of PEG 20000 in SDs. Mean dissolution time (MDT) of glimepiride decreased significantly after preparation of SDs and physical mixture with PEG 20000. The FTIR spectroscopic studies showed the stability of glimepiride and absence of well-defined glimepiride-PEG 20000 interaction. The XRD studies indicated the amorphous state of glimepiride in SDs of glimepiride with PEG 20000.