Abstract: AimTo prepare solid lipid nanoparticles by microemulsion technique. MethodsStearic acid was used as the oil phase, lecithin as surfactant, alcohol as cosurfactant and distilled water as the aqueous phase. Microemulsion was prepared by mixing the above component in proper ratio. The corresponding pseudo-ternary phase diagram monitored Microemulsion formation field of different lecithin/alcohol. Solid lipid nanoparticles (SLN) were prepared by dispersing warm microemulsion in cold water under magnetic stirring. Then appropriate microemulsions that can contain more water phase and suitable oil phase were selected to prepare SLN. The influence of formulation, process variables on the preparation and quality of SLN were studied. Based on the investigation of single factors, orthogonal design was used to optimize SLN formulation and preparation process, and more, the reproducibility of the optimized results were studied. ResultsThe results showed that the device temperature (T_i), water temperature (T_w), and delivery rate (r_d) were the key factors that influence the preparation process of SLN, and T_w was extremely important. The ratio of microemulsion formulation, the ratio of microemulsion and distilled water had also influence on its quality. Conclusion Microemulsion technique can be used to prepare solid lipid nanoparticles.