Objective: In the present protocol, employability of polymethacrylate polymer Eudragit RS100 for development of microparticles of water-soluble drug with desired values of response variables was investigated by central composite optimization design through the application of Design Expert ® Methods: The microparticles were developed by emulsion solvent evaporation process employing Eudragit RS100. Two effective independent variables drug: polymer ratio and stirring speed were selected to assess performance prospective of Eudragit on mean particle size, entrapment efficiency, percent yield and drug release in 12 h of microparticles. Thirteen batches generated by the software were prepared and subjected to different characterization test parameters obligatory for the evaluation of formulation. Validation of optimization model and Statistical interpretation of results was done using Analysis of Variance (ANOVA). software (Series DX10).Results: ANOVA indicated that the independent variables had a significant effect on response variables. Optimized formulation demonstrated close agreement amongst experimental and predicted responses with high desirability factor. In vitro drug liberation study for optimized formulation proposed a sustained release of drug from microparticles. Conclusion:In conclusion, the optimization technique was imperative in indicating the efficient applicability of Eudragit RS100 polymer in controlling the drug release of hydrophilic drugs.