This paper investigates, for the first time, the breaking mechanism of particles exposed to implosions of stable and transient cavitation bubbles via Kapur function analysis. The effect of ultrasonic frequencies of 30−1140 kHz and powers of 4−200 W on particle breakage of paracetamol crystals was studied. The dominant cavitation bubble type was defined via sonoluminescence measurements. The breakage rate of seed crystals with a median size of 75 μm was found to be independent of the applied power when ultrasonically generated stable cavitation bubbles were generated. Furthermore, a particle size threshold of ca. 35 μm was observed. The particle size could not be reduced below this size regardless of the applied power or frequency. For transient bubbles, in contrast, higher powers lead to considerably smaller particles, with no threshold size within the investigated power range. The Kapur function analysis suggests that stable bubbles are more efficient than transient bubbles to break coarse particles with sizes above 40 μm. Finally, cumulative breakage functions were calculated, and it was observed that transient bubbles generate more abrasion than stable bubbles.

This paper presents a study on the effect of ultrasonic frequency on both the nucleation and the degradation of paracetamol under sonication. The effect of ultrasonic irradiation was investigated for frequencies ranging from 41 to 1140 kHz. The results obtained in this paper show that the lower ultrasonic frequencies are preferable, both to enhance the nucleation rate and to limit degradation. A reduction of the metastable zone width was observed in all experiments when applying ultrasound. The highest reduction was achieved at a frequency of 41 kHz and a decrease of the reduction was observed with increasing ultrasonic frequencies. Degradation was limited at a frequency of 41 kHz, while significantly higher levels of degradation are observed at higher frequencies. Radical formation seems to be the main degradation mechanism for all frequencies.

Crystallization is an important and widely used separation technique in the chemical and pharmaceutical industry. Control of the final particle properties is of great importance for these industries. The application of ultrasound in these crystallization processes, also referred to as sonocrystallization, has shown to impact nucleation, crystal growth and fragmentation. As a result this technology has potential to control the final particle size, shape and polymorphic form.This review provides a comprehensive overview of the recent advances in sonocrystallization. It reviews the observed effects of ultrasound on the different stages of the crystallization process. Recent insights in the mechanism behind these effects are discussed as well. Finally, guidelines for the operating conditions, such as ultrasonic frequency, power, type of cavitation bubbles, time window and moment of application are formulated.