This study aimed to optimize and characterize formulation factors in the preparation of drug-loaded polymeric nanoparticulate drug delivery system by employing response surface methodology (design of expert-DOE). Nanoparticles were prepared by three different methods namely solvent evaporation, solvent diffusion, and cross-linking method. Effect of important factors like method of preparation, surfactant type, stabilizer type on particle size, and percentage entrapment efficiency were studied using DOE. The prepared formulations show particle size and % entrapment efficiency in the range of 602.11 ± 12.5 to 1005.55 ±98.6 nm and 77.01±0.003 to 97.01±0.21% respectively. Based on the result formulation prepared with nonionic surfactant (Tween 80), synthetic polymeric stabilizer (poly vinyl alcohol-PVA) and solvent evaporation method were found to be effective. After selection of optimized formulation, twelve formulations were prepared by altering key processing parameters like stabilizer and surfactant concentration and effective formulation was selected on the basis of in vitro release. Among various concentrations, formulation with combination of 0.50%