TY - JOUR
T1 - The influence of solute concentration and filtration on mesoscale clusters of flufenamic acid, a typical pharmaceutical compound, in ethanol
AU - Barua, Harsh
AU - Cookman, Jennifer
AU - Svärd, Michael
AU - Rasmuson, Åke
AU - Hudson, Sarah P.
N1 - Publisher Copyright:
© 2024
PY - 2025/4
Y1 - 2025/4
N2 - 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.
AB - 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.
KW - Crystallisation
KW - Dynamic light scattering
KW - Filtration
KW - Flufenamic acid
KW - Mesoscale clusters
KW - Nanoparticle tracking analysis
KW - Pharmaceutical drug
UR - http://www.scopus.com/inward/record.url?scp=85214259512&partnerID=8YFLogxK
U2 - 10.1016/j.jcis.2024.12.170
DO - 10.1016/j.jcis.2024.12.170
M3 - Article
AN - SCOPUS:85214259512
SN - 0021-9797
VL - 683
SP - 622
EP - 631
JO - Journal of Colloid and Interface Science
JF - Journal of Colloid and Interface Science
ER -