Unraveling the droplet drying characteristics of crystallization-prone mannitol – experiments and modeling

Spray-dried mannitol is a potential lactose replacement in pharmaceutical formulations, yet the drying behavior of individual mannitol droplets within the spray chamber has not been fully understood. This work explored the drying characteristics of mannitol by employing the reaction engineering approach (REA) in data analysis. A glass filament single droplet drying technique was used to monitor the changes in droplet temperature, mass, and diameter. The drying kinetics data obtained clearly demonstrated the droplet “wet-bulb” period, the crust formation, and the crystallization phenomena. The master activation-energy curves developed from REA modeling responded sensitively to varying drying temperatures, which could have led to different crystallization events. The deviation of these plots from the expected norms that do not encounter a phase change was used effectively to discern the physics involved. A REA kinetic model was proposed to assist in process optimization of large-scale spray-drying operations.