The administration of Lipid nanoparticles (LNP) by different routes involves technological challenges, particularly those associated to sterilization and stability. Publications suggest the stability of LNP formulations throughout harsh production conditions involved in pharmaceutical procedures is highly dependent on the type of surfactant used. Therefore, the capacity of tripalmitin-based LNP to withstand moist heat sterilization and freeze -drying has been evaluated using poly(vinyl alcohol), soya lecithin, polysorbate 20 and sodium deoxycholate as emulsion stabilizers. For comparison purposes a formulation containing diethylene glycol monoethyl ether (Transcutol ® CG) was also studied. Formulations were submitted to autoclaving (at 105ºC or 121ºC), fractiona l sterilization (80ºC/10 min/3 days or 60ºC/30 min /3 days), freeze -drying, and stored at 5±3°C for 6 months. Physical stability was evaluated using relevant parameters such as particle size, polydispersion index (PI) and zeta potential. Thermal analysis and dynamic light scattering studies were performed and the effect of parabens was also investigated to assess its influence on physical stability. The type of emulsifier plays a crucial role on the physical stability of LNP exposed to moist-heat sterilization and freeze-drying, but the inclusion of a liquid lipid had a clear stabilizing effect.Stability also improved after the addition of parabens, especially the formulation containing lecithin. Practical applications:The physical stability of LNP throughout relevant harsh processes, such as moist heat sterilization and freeze-drying, is still an issue that needs further technological studying. Nevertheless, this work demonstrates that suitable and stable LNP may be prepared and exposed to moist heat sterilization and freeze -drying, depending on the type of emulsifier. The use of a liquid lipid contributed to stabilize the tripalmitin-based LNP. Finally, formulations prepared with parabens present during emulsification were more stable than those supplemented with preservatives after preparation.