Tailoring the crystal size distribution of an active pharmaceutical ingredient by continuous antisolvent crystallization in a planar oscillatory flow crystallizer

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Cruz, P (Author) Other; Alvarez, C (Author) Other; Fernando Rocha (Author) FEUP; Ferreira, A (Author) Other

Journal

Title: Chemical Engineering Research and Design

Vol. 175

Pages: 115-123

ISSN: 0263-8762

Publisher: Institute of Chemical Engineers

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Other information

Authenticus ID: P-00V-DWS

DOI: 10.1016/j.cherd.2021.08.030

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9