Modelling particle breakage in in-line fluidic devices: Application to wet mill, ultrasonic horn, and vortex-based cavitation device

Particle size distribution (PSD) of active pharmaceutical ingredients (APIs) is often controlled by using in-line fluidic devices and mills. In this work, we have investigated the kinetics and mechanisms of particle breakage of organic crystals in three different milling devices by considering paracetamol as a model API. A population balance model was developed to model breakage of paracetamol particles in wet mill, ultrasonic horn, and vortex-based cavitation device. Breakage rate formulation considering two breakage mechanisms is proposed, which shows excellent agreement with experimental breakage rates reported in the literature. A binary daughter distribution function was proposed, which changes its shape and, thus, the breakage mechanism, depending on the parent particle size. Specific breakage rates and cumulative distribution functions were compared with the experimental data. The model was shown to describe experimental results for the three devices and different operating conditions. The model shows that higher (than that estimated from the experimental data) specific breakage rates need to be used for small particles for fitting the experimental data. This is likely to be because of representing multiple fragmentation occurring in experiments by binary breakage in the model. The presented results provide a useful tool for modelling particle breakage in fluidic devices. The approach and presented model provide a sound basis for modelling particle size distribution in crystallizers coupled with in-line particle breakage devices.