Crystallization from solution is a common unit operation for separating chemical species and producing solids with specific properties. Effective design and scale-up of crystallization requires an understanding of solid-liquid phase behavior and the kinetics of particle formation. This talk will present a workflow for developing crystallization processes based on the following key steps:
1. Define the product. The crystal structure, purity, size and shape impact the product performance and ease of processing or formulation.
2. Select a solvent. The solvent impacts both the phase behavior and crystallization kinetics and therefore affects the process yield, throughput, and product properties.
3. Characterize the phase diagram. The phase diagram dictates the mode of operation and defines the operational window to avoid excessive nucleation, formation of undesired solid forms, and liquid-liquid phase splitting (oiling out).
4. Select mode of operation and mode of initiation. The mode of operation and the method for initiating crystallization impact process variability, scalability, and operability.
5. Determine operating conditions. Operating rates and mixing conditions determine the supersaturation trajectory in the phase diagram, thus influencing the relative rates of nucleation, growth, and agglomeration that control the evolution of the particle population.
Within the context of this workflow, this talk will provide guidance on appropriate experimental, analytical, and modeling tools for effective design and scale-up. Application of the workflow will be illustrated using case studies from crystallization process development work at The Dow Chemical Company.
