Particle Size Control during Ultrasonic Cooling Crystallization of Paracetamol

Abstract The effect of ultrasound on the crystal size during cooling crystallization of paracetamol was investigated. Sonication was enabled in three distinct stages to define the operating guidelines for crystal size control. In addition, it was identified whether size reduction results from a higher amount of nuclei upon primary nucleation or from enhanced secondary nucleation. The results show that tuning of the ultrasonic power density and exposure time after nucleation results in crystal sizes between 70 and 140 µm. In contrast, the use of ultrasound before nucleation does not affect the size, indicating enhanced secondary nucleation as the main mechanism. Finally, sonication after complete desupersaturation reduces the crystal size by about 30 µm but causes surface erosion.