Spherical Pulverization—Design of Spherical Drug Particles by Mechano-Fused Granulation/Spheronization Technique

Abstract

The novel dry milling technique, i.e. “spherical pulverization”, has been developed by using a mechanical powder processor. It was found that the model drug crystals with more than 100 μm in diameter were well pulverized by co-processing with fine particles of corn starch (CS). The morphological observation and particle size evaluation revealed that the processed products formed the composite particles with ordered-mixed structure, having double-layered particles with a core of CS and a coating layer of drug crystals. This result suggested that the drug crystals were selectively micronized and the resultant miniaturized drug particles were adhered/fixed on the surface of un-milled CS particles. The mechanical characteristics detected by the indentation test assumed that the brittle drug crystals sandwiched between elastic CS particles would be successfully crushed down by high shearing stress in the processor. The dispersion-sedimentation test indicated that the fine drug particles were immediately detached from the composite particles in aqueous phase, constructing the fine suspension. The dissolution behavior from the processed particles was found to be improved and strongly dependent on the size and amount of detached drug particles. These results would propose the contamination-free dry milling technique without using hard milling balls or beads.

Graphical Abstract