Present investigation describes preparation of microspheres by solvent evaporation followed by in vitro characterization of microspheres to evaluate the effect of method of preparation on physical properties and drug release profile of microspheres. The microspheres were found to be discrete, spherical with free flowing properties. The morphology (Scanning Electron Microscopy), particle size distribution, entrapment efficiency and their release profiles were investigated. The yield was found to be maximum in case of solvent evaporation method. The microsphere prepared by solvent evaporation method was found in ranges of 250-50 μm, respectively. The microspheres formulation prepared by solvent evaporation method the drug carrier interactions were investigated in solid state by Fourier Transform Infrared (FT-IR) spectroscopy study. In vitro drug release rate for A microsphere was found to be sustained over 12 hours. Hence, it can be concluded that the Formulation prepared by solvent evaporation method, has potential to deliver Losartan Potassium in a controlled manner in a regular fashion over extended period of time in Comparison to all other formulations and can be adopted for a successful oral delivery of Losartan potassium for safe management of hypertension.