Lecithin and parabens play a crucial role in tripalmitin-based lipid nanoparticle stabilization throughout moist heat sterilization and freeze-drying

The administration of lipid nanoparticles (LNP) by different routes involves technological challenges, particularly those associated with sterilization and stability. Publications suggest that the stability of LNP formulations throughout the 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 (R) CG) was also studied. Formulations were submitted to autoclaving (at 105 or 121 degrees C), fractional sterilization (80 or 60 degrees C/ 30 min/3 days), freeze-drying, and stored at 5 +/- 3 degrees C for 6 months. Physical stability was evaluated using relevant parameters such as particle size, polydispersion index (PI), and xi 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 in 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.