Optimization Of Size Distribution Research Articles

Wet Milling, Seeding, and Ultrasound in the Optimization of the Oiling-Out Crystallization Process

Complicated solution environments in oiling-out crystallization can lead to particle agglomeration with wide size distribution and low purity of the products, due to complex interactions among two liquid phases and one solid phase during the oiling-out crystallization. This research mainly focuses on the optimization of size distribution by controlling particle agglomeration during the oiling-out crystallization process in a model system of propyl paraben–ethanol–water. Nucleation control technologies, wet milling, seeding, and ultrasound were used to limit the agglomeration. Further investigations of wet milling were performed before the nucleation or in the crystal growth stages with different geometries, such as coarse, medium, and fine rotor–stator tooth pairs. An integrated process analytical technology tools (PAT) array, including focused beam reflectance measurement (FBRM), particle visual monitoring (PVM), and attenuated total reflectance ultraviolet/visible (ATR-UV/vis), was used to observe the droplet formation of the dispersed phase, size distributions, and particle shapes during the nucleation and crystal growth. The results demonstrate that wet milling, seeding, and ultrasound technologies can help to optimize the particle size distribution in complex solution environments with different levels of efficiencies.