The microspheres, A natural biodegradable polymer, is of great interest in pharmacy research due to its excellent properties including bioavailability, no toxicity, high charge density and mucoadhesivity, which creates immense potential for various pharmaceutical applications. It has been studied as a promising carrier system for mucoadhesive drug delivery via nasal route to enhanced bioavailability.rnPreparing microspheres which will help in releasing small quantity of drug and thereby reduces the intensity of adverse effect associated with the drug, slowly dissolving polymer for sustaining the release may be suitable for long term therapy is controlled alleviation of clinical manifestation. Microspheres are evaluated by percentage yield, determination of percentage drug content, entrapment efficiency and in-vitro dissolution studies. The purpose of this research work was to develop optimized and systematically evaluate performances of microspheres of antiemetic drug ondansetron. Alginate microspheres coated with polymer pectin, starch corn were prepared by ionotropic- gelation technique utilizing various cross linking agent like calcium chloride (CaCl2) and (BaCl2), depending upon the variability in the concentration of alginate, percentage of cross linking agent, time of curing, the factors like particle size, incorporation efficiency and release rate of microspheres varies. The microspheres obtained were discrete, spherical and free flowing. rnAim of our present study was to formulate the Alginate Microsphere loaded with Ondansetron by using Ionic- gelation technique for control prolonged release of drug. Ondansetron Microspheres were formulated by using drug with Sodium alginate, Pectin and Starch in 9 formulations was f1, f2, f3, f4, f5, f6, f7, f8, f9. All the formulation were investigation for various evaluation parameters like Particle Size (360 to 280), Bulk Density (0.55 to 0.46 gm/ml) , Flow Behavior, Entrapment Efficiency (72 to 85%), Percentage yield (55 to78%), and In-vitro drug release etc. All the formulation showed good flow behavior. SEM Study revealed that the spheres were almost spherical in shape with smooth surface. In-vitro drug release study showed that by increasing the polymer concentration the drug release of all the formulation were gradually decreased and the optimized formulation (f3) was able to sustain the drug release for 12 hours. So, It was Concluded that Alginate Microspheres loaded with Ondansetron can be prepared by Ionic-gelation technique and used for sustaining the drug release for prolong period of time.