Development of Solventless Drug Pelletization Using a High Shear Granulator and Its Application to Pharmaceutical Amorphous Formulation

Abstract

This paper described a review of solventless pelletization using a high shear granulator to produce drug-layered pellets by simply mixing drug crystals and inactive spheres without using solvents and heating. High shear mixing of acetaminophen crystals and microcrystalline cellulose spheres resulted in pulverization of the drug particles due to collisions with the spherical cellulose in the granulator (i.e. ball-milling action) and the micronized drug particles were deposited on the spheres. High shear mixing of crystalline indomethacin and cellulose spheres led to mechanical activation of the drug due to ball-milling actions of the spheres, as well as pelletization, yielding amorphous drug-layered pellets. The pellets exhibited supersaturation characteristics. The amorphous drug deposited on the pellets exhibited a low physical stability but recrystallization could be inhibited by co-processing with amorphous stabilizers including polymer and amino acids. This technique contributes to simplification and cost reduction of pharmaceutical manufacturing processes.