Development of a novel pelletization technique through an extremely high-shear process using a mechanical powder processor to produce high-dose small core granules suitable for film coating.

We established an extremely high-shear melt pelletization technique using a mechanical powder processor to produce high-dose granules smaller than 300 μm with properties suitable for film coating. A mixture of ethenzamide and polyethylene glycol (used as a low-melting binder) at various weight ratios was mechanically treated under various jacket temperatures. When the jacket temperature was set to 50 °C or greater, the product temperature reached the melting point of the binder, resulting in pelletization. The drug powder were pelletized with a small amount of binder to yield pellets of approximately 150 μm with a drug content of more than 90%. The mechanism of melt pelletization through ultrahigh shearing involves a series of nucleation, consolidation, coalescence and breakage stages. The power consumption profile corresponding to each stage in the pelletization revealed that pellets between 75 and 300 μm were effectively obtained at a large power consumption peak. The resultant pellets showed comparative sphericity and smoothness, and higher durability than commercial core granules for film coating. In conclusion, this study demonstrates that the extremely high-shear melt pelletization technique can give drug pellets with desirable properties as core particles for the coating process.