Ensuring sufficient drug solubility is a crucial problem in pharmaceutical-related research. For water-insoluble drugs, various formulation approaches are employed to enhance the solubility and bioavailability of lead compounds. The goal of this study was to enhance the dissolution and absorption of a new cardiovascular lead compound, 26PH-1. Early-stage preparation discovery concept was employed in this study. Based on the concept, 26PH-1-loaded poly lactic co glycolic acid (PLGA) microspheres hold great potential as a drug delivery system for improving drug solubility and bioavailability. In this study, we used Shirasu Porous Glass (SPG) premix membrane emulsification technique characterized with high trans-membrane flux and size controllability to prepare uniform-sized PLGA microspheres. By optimized trans-membrane pressure and PVA concentration in external aqueous phase, uniform-sized PLGA microspheres with small size (around 5.3μm) were successfully obtained. Our results showed that using ultrasonication to form primary emulsion, microspheres with high encapsulation efficiency and appropriate in vivo release were achieved, the particle size determination was employed to confirm the formation of the microspheres. Scanning electron microscopy demonstrated that 26PH-1 was converted into an amorphous form. Finally, LC-MS/MS method for determining the concentration of 26PH-1 in plasma demonstrated that the bio-stability in microspheres was preserved during the preparation process.