Scale-Up

Scale-up refers to the process of transition crystallization methods from the controlled environment of laboratory benchtop experiments to full industrial-scale production. To ensure smooth scaling up, it is fundamental to understand its most critical parameter: mixing, which will influence the process attributes and performance. Mixing determines the effectiveness of heat and mass transfer, along with the phase dispersion characteristics. Mixing is influenced by several factors: crystallizer geometry, internal geometry and configuration, physiochemical properties of fluids and solids, and operating parameters 5. For a successful scale-up, it is crucial to ensure that local and global mixing conditions can be reliably reproduced as the transition from the laboratory scale to the pilot scale and, ultimately, to commercial production occurs. This replication is essential for maintaining process consistency and quality across different production scales.

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What issues arise during scale-up?

The scale-up process often faces challenges rooted in mixing and resultant complications, such as heat transfer, among others. As production moves from bench top towards industrial scale, the homogeneity achieved through mixing becomes more challenging to maintain. This can lead to uneven temperature and solute concentration distribution, which can be detrimental to the nucleation and crystal growth phases. This variability can result in non-uniform particle size distribution and shape anomalies, compromising quality and yield. The change in scale also typically affects heat transfer efficiency, as large volumes add an extra layer of difficulty for how the heat needs to be distributed or removed, complicating the maintenance of the precise temperature required for optimal crystallization.

Other factors impacted by scale-up include fluid dynamics and suspension behavior. This can affect, for example, the frequency at which fresh superheated solution is delivered to critical zones. This can drastically affect the supersaturation levels. These changes require meticulous testing to recalibrate these factors and be able to replicate the conditions achieved on smaller scales. Without careful adjustment and optimization of these factors, scale-up efforts can lead to increased production costs, extended development times, and even failure to meet regulatory and quality standards, posing substantial risks to commercial viability.

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