With the high-quality requirements for cephalexin monohydrate

developing a robust and practical crys-tallization process to produce cephalexin monohydrate with good crystal habit

appropriate aspect ratio and high bulk density as well as suitable flowability is urgently needed. This research has explored the influence of ultrasound on crystallization of cephalexin monohydrate in terms of nucleation mechanism and crystal habit control. The results of metastable zone width and induction time measurement showed the presence of ultrasound irradiation can narrow the metastable zone and shorten induction time. Cavitation phenomena generated by ultrasound were used to qualitatively explain the mechanism of ultrasound promoting nucleation of cephalexin monohydrate. Furthermore

on the basis of classical nucleation theory and induction time data

a series of nucleation-related parameters (such as crystal-liquid interfacial tension

radius of the critical nucleus and

etc

.) were calculated and showed a decreasing trend under ultrasound irradiation. The diffusion coefficient of the studied system was also determined to increase by 72.73% under ultrasound. The changes in these param

eters have quantitatively confirmed the mechanism of ultrasound influence on the nucleation process. In further

the calculated surface entropy factor has confirmed that the growth of cephalexin monohydrate follows continuous growth mechanism under the research conditions of this work. Through the exploration of crystallization conditions

it is found that suitable ultrasonic treatment

seeding

supersaturation control and removal of fine crystals are conducive to improving the quality of cephalexin monohydrate product. Optimizing the crystallization process coupled continuous ultrasound irradiation with fine-crystal dissolution policy has achieved the controllable production of monodisperse cephalexin monohydrate crystal with good performance.