Real-Time In-situ Imaging and Structural Characterisation of Continuous Crystallization in a Concentric-Flow Antisolvent Crystallizer

Our recent study (Diamond I13) showed that 2D X-ray Phase-Contrast Imaging provides high contrast and spatial resolution (~1µm) for real-time imaging of fast dynamic crystallization processes, giving a wealth of mechanistic insight into the nucleation and crystallization processes. We propose to conduct real-time diffraction-contrast and pair-distribution imaging studies of lovastatin crystallization in a concentric anti-solvent flow crystallizer as a function of concentrations and flow rates. Industrial manufacturing of lovastatin is challenging as it crystallizes as needles that are complex to process, so a deeper understanding of the relationship between crystallization conditions and crystal habit is required. The flow field in this crystallizer enables us to spatially separate mixing, supersaturated phase, nucleation and crystal growth. This permits unprecedented insight into the sequence of molecular and mesoscopic events that determine the properties of the crystalline product.