(222g) Development and Evaluation of Breakage Models for Needle-Shaped Particles: Accounting for Size and Aspect Ratio

In pharmaceutical manufacturing, solution crystallization often produces needle-shaped (acicular) particles with high aspect ratios. These particle shapes significantly influence both the drug’s bioavailability and key processing behaviors such as flowability and tablet formation. Consequently, accurately modeling particle shape evolution—particularly due to breakage—is critical for process design and control. However, existing models rarely account for how breakage alters particle shape.

This research focuses on developing enhanced population balance models to describe the breakage behavior of high aspect ratio crystals. Experimental studies using needle-shaped urea crystals agitated in dilute slurries demonstrated that breakage dynamics are sensitive to the breakage rate. Analysis revealed that the aspect ratio of resulting fragments is primarily governed by the major axis length of the child particles, with little influence from the minor axis.

Earlier simulation efforts included a simplified model assuming all particles break perpendicular to their major axis, as well as an empirical correlation relating the average aspect ratio of child particles to their major axis length. While both models aligned well with experimental data after one minute of breakage, their accuracy declined after five minutes, indicating limitations in their ability to capture longer-term shape evolution.

These findings demonstrate that the widely used assumption of binary breakage along a plane perpendicular to the major axis is insufficient for accurately predicting changes in particle shape. In response, this work introduces new two-dimensional population balance models—incorporating both particle size and aspect ratio—which are evaluated against each other and validated with experimental data.