In this work, we study changes in size and shape distributions, as well as number of particles during high shear wet milling, which is increasingly being employed for size reduction in crystalline slurries in pharmaceutical processing. Saturated suspensions of benzoic acid, paracetamol and metformin hydrochloride were used in this study. We employ our recently developed tools for estimating particle aspect ratio and particle size distributions from chord length distribution (CLD) measurements and imaging. We also compare estimated particle size distributions from CLD and imaging with corresponding estimates from offline instruments.
The results show that these tools are capable of quantitatively capturing changes in particle sizes and shape during wet milling inline. This is the first time that such a capability has been reported in the literature. The ability to quantitatively monitor particle size and shape distributions in real time will enable development of more realistic and accurate population balance models of wet milling and crystallisation, and aid more efficient control of crystallisation processes.
- particle size distribution
- chord length distribution
- wet milling