(423e) An Automated Crystallization-Filtration-Drying Workstation: Development and Application from the Perspective of Pharmaceutical Industry

Automated crystallization platforms have been pursued for more than two decades with the progress of process analytical technology (PAT) tools in the pharmaceutical R&D sector [1]. By manipulating solute concentration, supersaturation levels, and other parameters, crystallization mechanism and kinetics can be better understood to control crystal size, shape, morphology [2]. While fruitful achievements in academy and industrial applications have been reported [3], commercially off-the-shelf crystallization platforms or workstations are still not readily available or routinely deployed. Furthermore, downstream operations such as filtration and drying of the final crystalline product are often not integrated. Typically, the overall process cause-and-effect relationship in the fishbone diagram are not fully understood [4].

In this work, the development and application of an in-house automated crystallization-filtration-drying workstation for process development and engineering purposes will be discussed. This includes: (1) an automation I/O communication network to integrate the equipment, instruments/sensors, and mathematical models; (2) process monitoring and PAT-based feed-back control strategies for batch crystallization with cooling, antisolvent addition, or combined cooling and antisolvent addition; (3) wet cake filtration characterization; (4) drying kinetics under heated, vacuumed, and/or humidified conditions. Equipment design, automation, human-machine-interface (HMI), and considerations for further development will be discussed.

References

[1] Fujiwara M, Nagy ZK, Chew JW, Braatz RD. First-principles and direct design approaches for the control of pharmaceutical crystallization. Journal of Process Control, 2005; 15(5):493-504.

[2] Nagy ZK, Braatz RD. Advances and new directions in crystallization control. Annu Rev Chem Biomol Eng. 2012; 3:55-75.

[3] Gao Y, Zhang T, Ma Y, Xue F, Gao Z, Hou B, Gong J. Application of PAT-Based Feedback Control Approaches in Pharmaceutical Crystallization. Crystals. 2021; 11(3):221.

[4] Su Q, Ganesh S, Moreno M, Bommireddy Y, Gonzalez M, Reklaitis GV, Nagy ZK. A perspective on Quality-by-Control (QbC) in pharmaceutical continuous manufacturing. Computers & Chemical Engineering. 2019; 125: 216-231.