The goal of this study was to develop sustained-release microbeads containing Ranolazine. The Ranolazine was selected on the basis of its short half-life i.e., 1.5 h and used in treatment of Angina pectoris. The fundamental goal of this research is to increase duration of drug release. Ranolazine was encapsulated with natural polymers such as Hygrophila auriculata seed mucilage by an ionotropic gelation technique. The formulation batches were optimized with a 32 factorial design and physicochemical characteristics were also evaluated. The particle size of microbeads, entrapment efficiency of drug, surface morphology, In-vitro release of drug was investigated. The in-vitro studies of optimized microbeads formulation batch (B2) containing 100:600 ratio of Hygrophila auriculata seed mucilage and sodium alginate exhibited as a sustained release of Ranolazine up to 12 h and. The mucoadhesion potential was found to be 97± 1% up 12 h. In our perspective, the current ER pellet formulation might be the most feasible alternative to traditional pain management formulas. All the trial’s batches were shown to be suitable in extended release of a short elimination half-life medication with enhanced bioavailability, implying that it is useful for oral drug delivery. Keywords:  Design of experiment, Extrusion-spheronization, Ionic gelation, Microbeads, Ranolazine,