The purpose of this research was to design, formulate and optimize the floating microspheres of lercanidipine hydrochloride so as to prolong its gastric residence time and increase its bioavailability as it has less solubility. The solvent evaporation technique was used for preparing the floating microspheres and optimized using Box-Behnken design. The independent variables were the ethyl cellulose (X1), HPMC (X2), and stirring speed (X3) while Vesicle size (Y1), drug entrapment efficiency (Y2), and yield (%Y3) were considered as dependent variables. The prepared microspheres underwent the following in vitro evaluation tests, including those for micrometric properties, tapped density, particle size measurement, percentage yield, entrapment efficiency, in vitro buoyancy, and drug content