The purpose of this study was to investigate the effect of polymer and surfactant concentration on drug loading and in vitro drug release of micro particulate drug delivery system of Losartan potassium (LST). Microparticles were prepared by O/O solvent emulsification method. A 32 full factorial design was used to derive statistical equation and construct contour plots to predict responses. The independent variables selected were polymer concentration (A), surfactant concentration (B). Dependent variables were percentage drug loading (Y1) and percentage drug release at 12 h (Y2). The in vitro drug release profile of prepared microparticles was compared with marketed tablet formulation. The release profile of microparticles was found to be sustained as compared to the marketed formulation. The drug loading was found to be in the range of 15.32% (F6) to 22.27% (F5). FT-IR analysis revealed no drug excipient interference. The morphology of evaluated microparticles at −1 level was found to be spherical and smooth in nature while at higher level +1 it was found to be rough, irregular, with erosion, cracks and wrinkles on the surface. In XRD analysis crystalline pattern of pure LST was changed to amorphous pattern when converted to microparticles.