Polystyrene beads for efficient temperature control and drug nanoparticle production in wet stirred media milling

This study explores the effects of stirrer speed, bead loading, and bead size on the evolution of mill outlet temperature during the wet stirred media milling (WSMM) of fenofibrate suspensions using crosslinked polystyrene (CPS) beads. Key parameters, including mill outlet temperature, particle size, suspension viscosity, and power consumption, were systematically measured. Power-law correlations were established to link the normalized temperature rise and power consumption with process parameters, revealing that stirrer speed exerts the greatest influence on both metrics, followed by bead loading and size. Notably, all milling runs, even under the highest power density conditions, were completed in a single cycle, eliminating the need for intermittent milling. The maximum temperature rise observed was 25 °C. Moreover, a microhydrodynamic (MHD) model was developed to investigate the influence of process parameters on MHD metrics, establishing correlations between median particle size, dimensionless temperature, and MHD parameters. The results demonstrated that an increased average frequency of particle compression is directly associated with higher temperature rise and finer particle sizes, underscoring the role of MHD parameters in governing thermal behavior and particle size reduction. Furthermore, comparison with yttrium-stabilized zirconia (YSZ) beads showed that CPS beads generated significantly lower heat while achieving comparable particle size reductions, making them particularly advantageous for milling thermally labile drugs. This study highlights the suitability of CPS beads for efficient and controlled WSMM, providing a promising alternative to YSZ beads for applications requiring stringent temperature control.