(145f) Scale-up of Anti-Solvent Crystallization Using in Situ Tools and Computational Fluid Dynamics

The anti-solvent crystallization of benzoic acid from ethanol-water mixtures using water as an anti-solvent is presented. Previous work by this group has identified a satisfactory way to express the solubility curve for an anti-solvent system and has investigated the impact of process parameters (anti-solvent addition rate, agitation intensity and anti-solvent addition location) on the metastable zone width. The present work combines Focussed Beam Reflectance Measurement (FBRM), Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and Particle Vision and Measurement (PVM) to identify parameters for the scale-up of the crystallization from the 500mL scale to the 70L scale. Computational Fluid Dynamics (CFD) is used to investigate mixing regimes at both scales in order to identify suitable addition locations, feed regimes and agitation levels. A growth rate expression for the crystallization at the 500mL scale is calculated by combining the FBRM, to measure a growth rate, and ATR-FTIR, to monitor the supersaturation. The impact of process parameters on this growth rate is also assessed.