Application of Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) Technique in the Monitoring and Control of Antisolvent Crystallization

On-line attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and focused-beam reflectance measurement (FBRM) were used to monitor and control anti-solvent crystallization of paracetamol from an acetone-water mixture, which was conducted isothermally in a 1-L crystallizer with a flat bottom. After analyzing the particle size distribution (PSD) and transient relative supersaturation data from constant anti-solvent addition rate experiments, a simple calculation method for the set point of anti-solvent addition rate, to maintain constant supersaturation via ATR-FTIR, was developed and implemented for feedback control of unseeded and seeded crystallization. The results of the controlled feeding rate experiments show that the particle size and PSD, as well as the total batch time, can be favorably manipulated simultaneously.