Design and preparation of spherical particles in water via thermal-induced liquid-liquid phase separation and a molecular mechanism study

In the pharmaceutical and fine chemical industries, spherical particles are highly valuable due to their numerous applications; however, they are hindered by traditional methods requiring intricate devices, high energy consumption, and biohazardous solvents. In this study, we constructed a strategy for the design of spherical particles based on thermal-induced liquid–liquid phase separation at the microscopic molecular level. Based on this strategy, high-performance spherical particles were successfully prepared in water by a simple heating-quenching operation. Moreover, this strategy could also control the solid structure of particles by utilizing intermolecular interactions to meet the requirements of various application scenarios. In the case of fenofibrate, the equipment was simplified, the use of organic solvents was avoided, and the powder properties, filtration properties, and tableting performance of the product were significantly enhanced compared to those reported literature. This work elucidated the design and green production of new crystalline/amorphous materials with versatile functions.