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The influence of solute concentration and filtration on mesoscale clusters of flufenamic acid, a typical pharmaceutical compound, in ethanol
Department of Chemical Sciences, SSPC, the Research Ireland Centre for Pharmaceuticals, Bernal Institute, University of Limerick, V94 T9PX, Ireland.
Department of Chemical Sciences, SSPC, the Research Ireland Centre for Pharmaceuticals, Bernal Institute, University of 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, Transport Phenomena. Department of Chemical Sciences, SSPC, the Research Ireland Centre for Pharmaceuticals, Bernal Institute, University of Limerick, V94 T9PX, Ireland; .ORCID iD: 0000-0003-1790-2310
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2025 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 683, p. 622-631Article in journal (Refereed) Published
Abstract [en]

Hypothesis: It is hypothesised in this work that mesoscale clusters will be present in both undersaturated and supersaturated solutions of organic pharmaceutical molecules. These clusters, being loose aggregates, could be sensitive to shear forces experienced during filtration. Thus, comparing the behaviour of these clusters alongside nanoparticles during filtration—an important sample treatment parameter during crystallization—will elucidate qualitative differences from solid, crystalline nanoparticles of similar size. Experiments: The impact of filtration with different pore sizes and membranes on (i) mesoscale clusters of flufenamic acid (FFA) ethanol solutions and (ii) aqueous FFA nanosuspensions was studied with dynamic light scattering and nanoparticle tracking analysis. Findings: FFA solutions, ranging from undersaturated to supersaturated, were found to form mesoscale clusters, where the cluster size and number concentration were independent of solute concentration. Under filtration stress, irrespective of pore size and membrane used, the mesoscale cluster peak disappeared from the size distribution with no detectable change in concentration. In contrast, similarly sized FFA nanoparticles were removed by filtration, causing a significant change in solute concentration and size distribution. Mesoscale clusters of FFA in ethanol constitute only a tiny fraction of the total solute concentration and possess poor light scattering properties, lower mass density than solid particles of similar size, and no clear phase boundary.

Place, publisher, year, edition, pages
Elsevier BV , 2025. Vol. 683, p. 622-631
Keywords [en]
Crystallisation, Dynamic light scattering, Filtration, Flufenamic acid, Mesoscale clusters, Nanoparticle tracking analysis, Pharmaceutical drug
National Category
Physical Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-358400DOI: 10.1016/j.jcis.2024.12.170ISI: 001421831700001PubMedID: 39742743Scopus ID: 2-s2.0-85214259512OAI: oai:DiVA.org:kth-358400DiVA, id: diva2:1927875
Note

QC 20250303

Available from: 2025-01-15 Created: 2025-01-15 Last updated: 2025-03-03Bibliographically approved

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Svärd, MichaelRasmuson, Åke C.

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