(13a) The Application of Cfd to the Multi-Scale Characterization of Anti-Solvent Addition Crystallization

The anti-solvent crystallization of benzoic acid at 500mL, 2L and 70 L scales using different impeller geometries and addition modes is presented. Computational Fluid Dynamics (CFD) is applied to assess the mixing regime at each scale and for each impeller geometry. Focused Beam Reflectance Measurement (FBRM) Particle Vision and Measurement (PVM) were used to measure particle size and shape and Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) was used to monitor supersaturation.

CFD is used to assess, velocity profiles, tracer dispersion, mixing times and supersaturation profiles under all process conditions. This information is used to forge a link between the mixing regime in the vessel and the experimental data gathered using the in situ tools. The combination of these PAT tools allows for the production of a repeatable and robust crystallization, even in regions of poor mixing, and inturn has allowed for an overall increase in particel size. Thus reducing the impact on downstream processing such as filtration and drying, which is often a goal in the pharmaceutical industry.

Previous work by this group has identified the impact of addition rate and location, and agitation intensity on the crystallization characteristics. This work assesses the impact of feed pipe diameter and addition mode on the crystallization of benzoic acid, also exmained is the location of an 'optimum' anti-solvent feed point and the impact of various process parameters on particel size. This paper presents a semi quantatative method which allows for increased process understanding and a more robust scale up strategy.