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Effect of Solution Volume and Agitation on Primary Nucleation of Griseofulvin in Methanol
SSPC the Research Ireland Centre for Pharmaceuticals, Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland.
SSPC the Research Ireland Centre for Pharmaceuticals, Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemical Engineering, Resource recovery.ORCID iD: 0000-0002-6647-3308
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemical Engineering. SSPC the Research Ireland Centre for Pharmaceuticals, Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland.ORCID iD: 0000-0003-1790-2310
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2025 (English)In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 25, no 22, p. 9571-9580Article in journal (Refereed) Published
Abstract [en]

Nucleation, the first step of crystallization, is stochastic at small volumes and becomes increasingly deterministic with increasing volume. Translating crystallization processes from the lab to commercial scale remains challenging due to the stochastic nature of nucleation at smaller scales, differences between crystallizer designs, and inconsistencies that arise during scale-up. This study examines how solution volume and agitation affect nucleation kinetics in the crystallization of griseofulvin in methanol. Induction time experiments were conducted at 1 and 100 mL scales using Crystal16 and EasyMax setups, respectively. These results were compared to previously reported experiments conducted at a 20 mL scale using a setup of magnetically stirred solutions, where the induction time was determined through visual analysis of video recordings. GSF nucleated as stable Form I under all investigated conditions. There is a transition from stochastic nucleation observed at 1 and 20 mL scales to a more deterministic process at the 100 mL scale. The nucleation rate exhibits a correlation with differing energy dissipation and solution volume conditions.

Place, publisher, year, edition, pages
American Chemical Society (ACS) , 2025. Vol. 25, no 22, p. 9571-9580
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Bioprocess Technology
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URN: urn:nbn:se:kth:diva-373622DOI: 10.1021/acs.cgd.5c00495ISI: 001604991200001Scopus ID: 2-s2.0-105022200513OAI: oai:DiVA.org:kth-373622DiVA, id: diva2:2018885
Note

QC 20251204

Available from: 2025-12-04 Created: 2025-12-04 Last updated: 2025-12-04Bibliographically approved

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Svärd, MichaelRasmuson, Åke C.

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