Dry mixing transformed micro-particles of a drug from a highly crystalline to a highly amorphous state

In this paper, the degree of mechanical activation of particles due to mechanical straining without subsequent breakage has been studied. Griseofulvin micro-particles of about 2 microm in size were mixed with glass beads (proportion 1:99) in a tumbling mixer. After a series of mixing times, ranging from 2-96 hours, samples were withdrawn and the particle size and the degree of crystallinity were assessed. The mixing process gave no detectable change in particle size. The degree of disorder of the drug particles increased with mixing time and highly amorphous particles were obtained after about 24 h of mixing. The results thus indicate that particles can be completely activated by mechanical treatment without a parallel size reduction of the particles. It is suggested that the activation is caused by repeated deformation of the particles, gradually transforming the crystalline state into an amorphous state.