Abstract : Milling chamber filled with milling pearls, drug, stabilizer and dispersion media (e.g. water, buffer or organic solvent) are rotated in a milling machine at a very high speed. Under the movement of milling pearls, the collisions of the drug particles with milling pearls, milling chamber and other drug particles, together with high shear forces, fracture the drug crystals into nanosized particles. The common materials for the milling pearls include zirconium oxide, stainless steel, glass or highly cross-linked polystyrene resin. The process can be performed in batch or continuous modes. The range of milling time is from 30-60 min to several days for a batch of nanosuspensions, depending on the milling devices, milling parameters, batch size and components. Many factors affect the milling results, including the properties of the drug (e.g. hardness and density), concentration and type of stabilizer, viscosity of suspensions, amount of drug in the milling vessel, amount, diameter and density of milling pearls, and milling parameters (milling speed and time) .
