Optimization studies on mucoadhesive microspheres of felodipine for nasal delivery were aimed to modulate drug release, enhance residence time of microspheres and thereby improve the therapeutic efficacy of the drug undergoing extensive first pass metabolism. Mucoadhesive sodium alginate microspheres containing felodipine were prepared by emulsion-cross linking method. A 23 factorial design was employed for preparation of microspheres wherein the concentration of polymer, concentration of calcium chloride and cross-linking time were chosen as independent variables while particle size, % mucoadhesion and % drug permeation were taken as dependent variables. Amongst the cross-linking agents screened, calcium chloride was selected on the basis of particle size, regular shape and percentage yield. The microspheres, formulation F3 with least particle size of 39.9 µm, maximum in vitro mucoadhesion 79.98% and % drug permeation 94.8% were adjudged as optimized formulation. The experimental design was validated by extra design check point. SEM revealed the morphological characteristic of microspheres. DSC and XRD confirmed molecular dispersion of the drug in the microspheres polymeric matrix. DRS revealed no chemical interaction between the drug and polymer used. Histological study asserted no damage to the sheep nasal mucosal structure when incubated with F3. The formulation was found to be stable for a period of 3 months.