The effect of crystal imperfections on particle fracture behaviour.

Micronisation of active pharmaceutical ingredients is a process which is sometimes difficult to control. The main purpose of this study was to assess the effect of the pre-existing flaws in the material to be milled. The rate of breakage of four samples of a model compound (sodium chloride), originating from different sources, was determined in a jet mill. It appeared that each type of sodium chloride has a distinct particle rate of breakage and breakage pattern. The numbers of flaws in the different types of sodium chloride have been determined by immersing the sodium chloride particles in a liquid with the same refractive index. This makes the cracks better visible. Microphotographs were made and flaws were counted manually. The study shows that the flaw density has an impact on the fracture behaviour of particles. The degree of fracture tends to increase with increasing flaw density. The paper shows however that the mechanical properties of the material as well as the starting particle size dominate the significance of the impact of flaws on fracture behaviour.