(368l) Development of Intensified Crystallization Systems through Modularization and Digital Design

Crystallization is a crucial process in various industries for solid materials serving as both a purification step and a means of controlling critical quality attributes (CQAs). These CQAs directly impact the quality and ease of subsequent operations. Efficient crystallization is essential for meeting industry standards, with continuous manufacturing offering streamlined operations and reduced supply chain vulnerabilities. Modular units enable local production and rapid adaptation to changing production needs, enhancing safety and flexibility.

This study proposes the creation of Modular Autonomous Crystallization Systems (MACS) that are controlled and automated via the in-house developed LabVIEW software, Omnibus. An (mixed-suspension, mixed-product removal) MSMPR-cascade was used as the model continuous system due to its compactness and a case study was completed to show the features of Omnibus including steady state detection and ability for intermittent transfer. Additionally, a full material case study is shown that required initial solubilities studies to be complete, as well as a concentration calibration. Using MACS to apply automated DoE through model-free quality by control (mf-QbC) to gain initial material kinetic insight through the valuable PAT tools. Based on this information a process model was developed to include the mechanisms occurring, allowing for parameter estimation to construct a digital twin using two-dimensional population balance modeling (2D-PBM). This digital twin facilitates in silico investigation of the design space and digital design of the crystallization process to achieve the desired CQAs. The results illustrate a systematic quality-by-digital-design (QbD²) framework for understanding and developing optimized crystallization processes.