Emulsion-assisted cooling crystallization of ibuprofen

The crystal size distribution (CSD) is an important quality attribute of pharmaceutical crystals. An emulsion is an attractive system to enable improved control over the CSD compared to conventional bulk crystallization by confining the crystal formation and growth. However, the method is currently challenged by inhibition of nucleation in small droplets and a lack of confinement of growing crystals. Cooling crystallization of a pharmaceutical inside the droplets of an oil-in-water emulsion is investigated. The droplet size is optimized to avoid the strong inhibition of nucleation and to minimize a lack of confinement of growing crystals. Furthermore, the influence of the type of surfactant and the hydrodynamic conditions on the CSD are investigated. The results demonstrate how the inhibition of nucleation in emulsion droplets due to the small-volume effect can be mitigated and how confinement can be improved, which is important for improved control over the CSD.