(470d) Use of in-Situ Instrumention to Characterise Anti-Solvent Addition Crystallization

Anti-solvent addition is an important crystallization technique that can be used as an alternative to cooling or evaporation.

Methods for the determination of nucleation kinetics in drowning out crystallisation using in situ instrumentation are presented. The crystallisation of benzoic acid from ethanol-water mixtures, with water acting as the anti-solvent, is the system studied. In situ Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) is used to monitor the liquid phase composition, specifically the concentration of benzoic acid in solution and the mass ratio of ethanol and water in the system. Lasentec Focused Beam Reflectance Measurement (FBRM) and Lasentec Particle Vision and Measurement (PVM) are used to monitor key properties relating to the size and shape of the crystals as they nucleate and grow. The effect of agitation and the rate of anti-solvent addition on the metastable zone width is investigated.

In general, the metastable zone width is wider at higher addition rates. However, at very high addition rates the metastable zone width does not widen and may even decrease. This is due to poor mixing in the vessel leading to a region of high supersaturation near the addition point and ultimately premature nucleation. The effect is exacerbated at low agitation values. Nucleation kinetics are calculated for all addition rates. The data from the runs carried out at low agitation levels appear to be unreliable due to poor mixing in the vessel. It appears that agitation has an effect on the nucleation kinetics.