Comparative Analysis of Polystyrene versus Zirconia Beads on Breakage Kinetics, Heat Generation, and Amorphous Formation during Wet Bead Milling.

Abstract

This study determined process conditions under which polystyrene (CPS) and zirconia (YSZ) beads cause similar breakage kinetics and temperature rise during manufacturing of drug nanosuspensions via wet bead milling and explored relative advantages of CPS beads, particularly for stress-sensitive compounds. Besides temperature and particle size measurements, a microhydrodynamic-based kinetic model simulated the conditions for CPS to achieve breakage rates equivalent to those of YSZ. A power law correlation was applied to find conditions conducive to temperature equivalency. The maximum contact pressure and pseudo energy dissipation rate were calculated under these equivalency conditions. When bead loading for CPS was increased to match with YSZ, lower temperature at similar breakage conditions or faster breakage at the same temperature was achieved. Increasing the tip speed did not provide any notable advantages for CPS over YSZ in terms of breakage kinetics or temperature. However, under all conditions investigated, CPS beads exhibited markedly lower maximum contact pressure and pseudo energy dissipation rate, which may correlate with reduced mechanically induced amorphization during milling. A proof-of-concept study demonstrated that a mechanical stress-sensitive drug had lower amorphous generation with CPS compared to YSZ. Therefore, CPS beads are a promising alternative to YSZ beads, especially when used at the highest feasible loading.