Heterogeneous Nucleation of Small Molecule Crystals in the Presence of Nanoparticles

Heterogeneous nucleation is a phenomenon of fundamental relevance in any laboratory or plant setting due to the ubiquitous presence of surfaces (such as the crystallizer walls, the impeller or dust), which lower the energy barrier to crystal nucleation. However, the physical mechanisms underlying heterogeneous nucleation have not been fully elucidated yet. In this work, we investigate the crystallization of active pharmaceutical ingredients in the presence of nanoparticles, which are particularly well suited to study surface effects due to their large surface area and their tunable properties (in terms of size, shape and surface chemistry). We perform our studies with silica coated magnetic nanoparticles, either bare or functionalized with various silanes. We follow the crystallization process at different levels of supersaturation with focused beam reflectance measurements and we show that the presence of nanoparticles impact both the kinetics of crystallization and the crystal size distribution. In addition, we find that the incorporation of nanoparticles in the crystal lattice is strongly related to the surface functionalization.