Particle engineering in anti-solvent crystallization

Abstract

Particle engineering in anti-solvent crystallization is explored in this thesis using paracetmaol-acetone-water as the model system. Particle size distribution and agglomeration degree are the two target solid-state attributes to be engineered. Process analytical technologies, including attenuated total reflectance Fourier Transform of Infrared spectroscopy (ATR-FTIR), focused beam reflectance of measurement (FBRM) and PVM are employed to monitor and control the process.Agitation intensity and feeding rate of anti-solvent were identified as the most important operating factors for the model system. ATR-FTIR is employed to construct a feedback control platform for supersaturation by which the feeding rate of anti-solvent is adjusted on-line to achieve constant-supersaturation operation. It is demonstrated that coefficient of variation of PSD, average particle size and batch time can be optimized more easily with feedback control of supersaturation than with constant feeding rate of anti-solvent. A procedure to formulate seeding policy under constant supersaturation is proposed.