(12d) Online Particle Size Measurement in a High Pressure Antisolvent Process

The particle formation in a supercritical antisolvent (SAS) process is influenced by thermodynamics, fluid mechanics and precipitation kinetics. Varying these process conditions therefore leads to the generation of differently sized and shaped particles. The produced particles are usually separated by filtering and then characterized under atmospheric conditions by offline measurement techniques. SEM images, X-ray diffraction patterns and particle-size distribution curves are the tools currentlyused. In this contribution an online particle size measurement technique based on dynamic and spectral extinction measurement is applied for determination of mean particle size at different process conditions under high pressure and for monitoring the particle growth in a cascaded spray process. The technique is applicable for particle sizes in the range of 60 nm to 200 µm.

After a short introduction of the measurement principle, experimental results of the online particle size measurement in a SAS batch process are presented and verified SEM images. The application range of the measurement technique for high pressure spray processes is discussed. The presented experiments were performed with dissolved paracetamol (acetaminophen) or ascorbic acid in ethanol, which was dispersed into supercritical CO2 by two different injection devices (nozzle and capillary) with different injection pressures at several operation pressures. Starting from this basic operation procedure, a particle growth was additionally induced by consecutive spray pulses into a particle suspension and the reproducibility of the spray process was finally examined at different operation conditions. The results demonstrate that the online measurement technique is a capable tool for inline-characterization and for determine the particle size variation due to changing process conditions. This allows a particle size adjustment, which might be an interesting aspect in pharmaceutical applications.