An active pharmaceutical ingredient is currently produced in a traditional batch antisolvent crystallization process. Although well-established, this process lacks flexibility to control the crystal size distribution (CSD). Therefore, a new process was developed to enable the control of the CSD according to different specifications. This new process was implemented in continuous in a planar oscillatory flow crystallizer (planar-OFC). In this work, the main goal was to enable the production of small crystals to meet very specific formulation requirements and, simultaneously, promote the aggregation of these small particles to optimize the filtration operation. First, the operating conditions were optimized for continuous operation. Then, the planar-OFC was divided into two spatially independent sections, the nucleation zone (where nucleation is dominant) and the crystal growth zone (where crystal growth is dominant), so as to control the CSD as a function of the residence time in each zone. In particular, the formation of aggregates could be promoted by increasing the residence time in the nucleation zone. Ultimately, the planar-OFC was able to produce smaller particles with significantly narrower CSDs than the traditional batch process. This is particularly important when small particle sizes are required, thus reducing manufacturing time and operating costs. (c) 2021 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.

• University of Porto
• Hovione Farmaciencia SA

• API

1. Active pharmaceutical ingredient
2. Aggregation
3. API
4. Continuous crystallization
5. Crystal size distribution
6. Planar oscillatory flow crystallizer
7. Research Article