Ultrasonic spray freeze-drying of sucrose and mannitol-based formulations: impact of the atomization conditions on the particle morphology and drying performance

Spray freeze-drying is an emerging manufacturing technology that offers many advantages, including long-term stability, consistent particle size distribution, and enhanced bioavailability. However, its implementation on an industrial scale is still hampered by several technical problems relating to the design of the equipment and the selection of appropriate operating conditions. This study aims to clarify the relationship between the atomization conditions (atomizing power, feed flow rate, and viscosity) and the characteristics of the lyophilized powder (particle size distribution and morphology) for two model products (sucrose- and mannitol-based formulations). Independently of the formulation, the particle morphology only depended on its solid content, while the average particle size increased with the feed flow rate and viscosity. Lastly, the specific surface area of the lyophilized powder varied with the initial solid content and the type of excipient as well, with mannitol-based particles having the highest specific surface area.