Novel contamination-free wet milling technique using ice beads for poorly water-soluble compounds

The aim of this study is to establish a contamination-free milling method using ice beads instead of conventional hard beads such as metal or ceramics. Ice beads, which melt after the milling process to form water, would solve the contamination issue attributed to bead breakage or abrasion. The technique/method for preparing spherical ice beads of mono-dispersed size ranging from 150 to 3000 μm was newly developed. An oscillation beads milling apparatus was used for pulverization. In the initial stages of ice beads milling, the process is dry, but as time passes, the surface of the ice beads begins to melt, resulting in a transition to wet beads milling. It was found that ice beads are an effective milling media for beads milling, and that milling efficiency is strongly affected by the temperature of the coolant, with the peak efficiency occurring when the temperature was set to -2 °C and ice beads around 1500 μm in diameter were used. The spray-dried powder obtained from suspension after ice beads milling had dissolution improvement equivalent to that obtained after zirconia beads milling, resulting from its spontaneous rapid dispersion into nanosuspension.