At the early stage of new drug development in pharmaceutical industry, the quantity of powder available is usually small. The oscillatory single ball mill or other similar machines are attractive in identifying the milling requirements, provided there is sufficient understanding of the milling process in these devices. This work aims at developing a fundamentally generic approach to achieving the selection in a more predictive way. The methodology used here is through relating the measured bulk milling performance in terms of a parameter called milling rate constant (Kp), to the input energy obtained through numerical simulations using the distinct element method (DEM).

Two commonly used pharmaceutical excipient powders, i.e. microcrystalline cellulose and á-lactose monohydrate have been milled in an oscillatory single ball mill. Effects of feed particle size, milling frequency and milling duration on the materials have been examined. These allow the milling rate constant (Kp) to be quantified.

The DEM simulations give trajectories of the milling media and the particles as a function of time and hence their velocity profiles. The milling energy is deduced from the relative velocities of objects coming in contact with each other. The simulated motions of the powder and the milling media in the jar agree with the experimental observations using a high-speed video camera with acquisition speed of up to 40,000 frames per second.

The milling results, characterised by the milling rate constant, has been found to correlate very well to the milling input energy, determined by DEM simulations. This provides an advancement towards development of a predictive methodology for selection of milling conditions, as well as milling device scale-up.