Abstract
In the pharmaceutical production field, it is required to produce organic fine crystalline particles having a monodispersed crystal size distribution (CSD). Anti-solvent crystallization is one method for producing crystal particles. In order to produce fine crystalline particles and/or crystals having 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 at a milli-sized segmented flow has been carried out to produce organic fine crystalline particles having a monodispersed CSD in the anti-solvent crystallization. Taurine (solute)–water (solvent)–EtOH (anti-solvent) system is employed. The effect of segmented flow on mixing solution has been observed with a high-speed microscope. Fine crystalline particles which have tens of microns average size are obtained with the integration of ultrasound irradiation and temperature modulation on a milli-sized segmented flow. Furthermore, crystals of 10 µm size are produced under controlled supersaturation condition. Additionally, it is suggested that the CSD could be improved by introducing temperature modulation after nucleation.
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