Aim: Objective of the present study to enhance the dissolution bioavailability of antidiabetic agent of class III sulfonyurea Glimepiride (GM) through synthesis of ternary solid dispersion (TSD) through alkalizers. Materials and methods: GM and TSD were synthesized by hot melt extrusion (HME) along Kollidon® VA64 using as carrier compound while Lysine/meglumine as alkalizer agents. The release of ternary solid dispersion in vitro was evaluating by dissolution and dissociation constant (pKa). Morphological study of the resultant modified drug observed by scanning electron microscopy (SEM), different scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) while kinetic study done by X-ray photoelectron spectroscopy(XPS), fourier transform infrared spectroscopy (FTIR), raman Spectroscopy (RS) and molecular docking. Results: Dissolution of GM notably elevated of TSD in comparison to pure GM and binary solid dispersion turned into amorphous shape with high ionic paired energy in TSD. TSD lower pKa value expresses that greater degree of ionization is good for dissolution of the GM. Conclusion: Modified forms of alkalizers proved beneficial in improving the dissolution of GM and exhibited a good potential in delivery systems of drug