Aim: Sulphasalazine (SSZ), an anti-inflammatory drug, has been widely used as a second line agent for Rheumatoid Arthritis. In this study Nanoprecipitation technique and Ionic gelation techniques were selected for the preparation of Sulphasalazine nanoparticles. Eudragit S100 and Ethyl Cellulose polymers were selected for nanoprecipitation technique and chitosan was chosen as a polymer for inotropic gelation method. A comparative study was performed.Methods: Sulphasalazine loaded Eudragit S100 and Ethyl Cellulose nanoparticles were prepared in five ratios varying the concentration of drug and polymer. Sulphasalazine loaded Chitosan- Tripolyphosphate nanoparticles were prepared by Ionic gelation technique in six ratios by varying the concentration of tripolyphophate solution as well as the concentration of the drug. Results: In nanoprecipitation technique, Out of the five formulations of EC and five formulations of Eudragit, F3 formulation of EC showed promising results with mean particle diameter of 165.3 nm and zeta potential of -47.7 mV with cumulative drug release of 97.89% in 12 h. In Ionic gelation method, out of six formulations, F6 formulation with 0.5% TPP and 4.687 mg/ml drug was considered as the best formulation because of its good stability(-43.8mV) and mean particle diameter (147.9 nm) which produced a sustained drug release of 97.92% in 12 h. Conclusion: On comparing the best formulations of both the techniques, nanoprecipitation was found to be the best technique because of its mean particlediameter (165.4 nm), greater stability (-47.7 mV) and higher drug entrapment efficiency (89.29%).