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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/26476

Title: Agglomeration Control during Ultrasonic Crystallization of an Active Pharmaceutical Ingredient
Authors: Gielen, Bjorn
Jordens, Jeroen
Thomassen, Leen C. J.
Braeken, Leen
Van Gerven, Tom
Issue Date: 2017
Citation: CRYSTALS, 7(2) (Art N° 40)
Abstract: Application of ultrasound during crystallization can efficiently inhibit agglomeration. However, the mechanism is unclear and sonication is usually enabled throughout the entire process, which increases the energy demand. Additionally, improper operation results in significant crystal damage. Therefore, the present work addresses these issues by identifying the stage in which sonication impacts agglomeration without eroding the crystals. This study was performed using a commercially available API that showed a high tendency to agglomerate during seeded crystallization. The crystallization progress was monitored using process analytical tools (PAT), including focus beam reflectance measurements (FBRM) to track to crystal size and number and Fourier transform infrared spectroscopy (FTIR) to quantify the supersaturation level. These tools provided insight in the mechanism by which ultrasound inhibits agglomeration. A combination of improved micromixing, fast crystal formation which accelerates depletion of the supersaturation and a higher collision frequency prevent crystal cementation to occur. The use of ultrasound as a post-treatment can break some of the agglomerates, but resulted in fractured crystals. Alternatively, sonication during the initial seeding stage could assist in generating nuclei and prevent agglomeration, provided that ultrasound was enabled until complete desupersaturation at the seeding temperature. FTIR and FBRM can be used to determine this end point.
URI: http://hdl.handle.net/1942/26476
DOI: 10.3390/cryst7020040
ISI #: 000395486800010
ISSN: 2073-4352
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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