Optimization of Nanoliposomes Production using a Coaxial Jet Mixer: a Response Surface Modeling Approach

Liposomes are vesicular structures capable of encapsulating and delivering active pharmaceutical ingredients or other compounds. A thorough understanding of their physical properties is essential for optimizing their application potential. In this work, liposomes were produced using ethanol, with phosphatidylcholine from soy lecithin processed via a coaxial jet mixer. The study investigated the effect of key operating parameters—ethanol flow rate, water flow rate, and phosphatidylcholine concentration—on four experimental responses: Z-Average, Polydispersity Index (PDI), Main Intensity Peak Size, and Zeta Potential. A Box-Behnken Design (BBD) was employed to optimize the experimental plan, minimizing the number of trials compared to a full factorial design. Measurements performed using a Zetasizer enabled the development of predictive models for the selected responses. Modeling results, based on a univariate analysis and a top-down approach, showed that within the explored parameter range, Z-Average was primarily influenced by the inner flow rate and phosphatidylcholine concentration. These parameters also significantly affected the Zeta Potential, while water flow rate had the least impact on the responses. To achieve smaller liposomes, the results indicate the need for low phosphatidylcholine concentrations combined with high inner flow rates.