Article ID: 11we168
In the pharmaceutical production field, it is required to produce organic fine crystalline particles which have a monodispersed crystal size distribution (CSD). Anti-solvent crystallization is one of the methods for producing crystal particles. In order to produce fine crystalline particles and/or crystals which have a monodispersed CSD, several methods such as segmented flow in the tubular crystallizer, ultrasound irradiation, and modulated operation in batch cooling crystallization have been studied in previous studies. In this study, integrated operation of ultrasound irradiation and temperature modulation to milli-sized segmented flow was carried out to produce organic fine crystalline particles which have a monodispersed CSD in the anti-solvent crystallization. The Taurine (solute)—Water (solvent)—EtOH (anti-solvent) system was used. The effect of segmented flow on mixing solution was observed with high-speed microscope. Fine crystalline particles which have a tens of microns average size were obtained with integration of ultrasound irradiation and temperature modulation to milli-sized segmented flow. Furthermore, crystals with 10 μm size were produced under controlled supersaturation condition. Additionally, it was suggested that the CSD could be improved by introducing temperature modulation after nucleation.
