Online measurement of particle size distribution during crystallization using ultrasonic spectroscopy

Particle growth during crystallization of paracetamol was monitored on-line using a new modified method based on ultrasonic spectroscopy. The model was earlier developed and tested with inert particles systems and accounts for low angle scattering and probe geometry. A graphic user interface was developed and integrated with the model based deconvolution algorithm for real-time data acquisition, analysis and display of results. The crystal growth and changes in size distribution were measured during the crystallization of paracetamol from paracetamol–isopropanol–water solution. A simplified pre-calibration procedure using acoustic velocity to estimate solution properties was established. The model based particle size distribution showed good agreement with offline measurements using laser diffraction analysis of a sample retrieved from the crystallizer.