Process intensification and control strategies in cooling crystallization: Crystal size and morphology optimization of α-PABA.

• The concentration calibration model is established to correlate the solubility. • Process intensification and control strategies are used to optimize the products. • Multi objectives optimization is achieved by the combination of techniques. This study explores the process intensification techniques and process control strategies on the product properties optimization. α-PABA, a long needle-like shape, can cause problems for the downstream processing. This study proposes ultrasound technique, supercooling control (SSC), and temperature cycling (TC) technologies to optimize the morphology and crystal size distribution of α-PABA. Firstly, the solubility and metastable zone of α-PABA in ethanol solvent are measured to determine the operational range. Next, the concentration calibration model is established to correlate the solubility with the ATR-FTIR intensity and temperature qualitatively. Furthermore, the process improvement techniques and control strategies are introduced to optimize the products. The ultrasound intensification contributes to produce the uniform crystal seeds. The SSC is benefit for the crystal growth, and can reduce the L/D ratio of the crystal product. While, TC is an efficient tool to eliminate the fine crystals. Moreover, the combination of ultrasound, SSC, and TC technology can show a significant improvement on the product particle aspects. The L/D ratio, crystal size, crystal morphology can show different degree of improvement under the combination techniques. At last, the outlook and perspectives on the process analytical technology are developed. [ABSTRACT FROM AUTHOR]