Utilizing crystal structures for predicting impact of mechanical and surface properties on particle fracture

The micronization process of new compounds is usually performed based on an empirical basis with a limited understanding of input material properties and potential challenges. This study focuses on the understanding of the fracture behavior of small organic molecular crystals, by using particle shape and surface energy analysis techniques as well as molecular modeling tools. These methodologies enable us to generate new data and new ways of working that can provide crucial information for future pharmaceutical development. The shape, surface energy, and mechanical properties for four different drug substances were studied. This study showed that the crystal shape and the intermolecular interactions influence the dominant fracture mechanism. An in-depth knowledge of these together with the mechanical properties gives an insight of the fracture mechanism of small organic molecular crystals. In a second part, Partial Least Squares regression was applied to the data sets to model the size reduction ratio and ...