Formation mechanisms of sub-micron pharmaceutical composite particles derived from far- and near-field Raman microscopy

Jakob Hübner; Jean-Baptiste Coty; Yan Busby; Denis Spitzer

doi:10.1016/j.jpha.2020.12.002

Volume 11 Issue 4

Aug. 2021

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Jakob Hübner, Jean-Baptiste Coty, Yan Busby, Denis Spitzer. Formation mechanisms of sub-micron pharmaceutical composite particles derived from far- and near-field Raman microscopy[J]. Journal of Pharmaceutical Analysis, 2021, 11(4): 480-489. doi: 10.1016/j.jpha.2020.12.002

Citation:

Jakob Hübner, Jean-Baptiste Coty, Yan Busby, Denis Spitzer. Formation mechanisms of sub-micron pharmaceutical composite particles derived from far- and near-field Raman microscopy[J]. Journal of Pharmaceutical Analysis, 2021, 11(4): 480-489. doi: 10.1016/j.jpha.2020.12.002

Citation:

Jakob Hübner, Jean-Baptiste Coty, Yan Busby, Denis Spitzer. Formation mechanisms of sub-micron pharmaceutical composite particles derived from far- and near-field Raman microscopy[J]. Journal of Pharmaceutical Analysis, 2021, 11(4): 480-489. doi: 10.1016/j.jpha.2020.12.002

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Formation mechanisms of sub-micron pharmaceutical composite particles derived from far- and near-field Raman microscopy

doi: 10.1016/j.jpha.2020.12.002

a. Nanomatériaux pour Les Systèmes Sous Sollicitations Extrêmes (NS3E), ISL-CNRS-UNISTRA UMR 3208, French-German Research Institute of Saint-Louis, 5, Rue Du Général Cassagnou, B.P. 70034, 68301, Saint-Louis, France;
b. Spinofrin SAS, 20 Bis Rue Danjou, 92100, Boulogne, Billancourt, France

Funds:

The authors thank their colleague Cédric Martin (Spinofrin SAS, Boulogne-Billancourt, France) for recording the presented SEM image. The Synthesis, Irradiation, and Analysis of Materials (SIAM), technological platform of University of Namur is acknowledged for XPS measurements. The authors also thank the Direction Générale de l’Armement (DGA, France) and the Bundesamt für Ausrüstung, Informationstechnik und Nutzung der Bundeswehr (BAAINBw, Germany). ISL is a joint initiative of the Ministère Armées (France) and the Bundesministerium der Verteidigung (Germany) and is actively supporting the NS3E joint laboratory including the Centre National de la Recherche Scientifique (CNRS) and the University of Strasbourg (UNISTRA).

Received Date: Apr. 13, 2020
Accepted Date: Dec. 02, 2020
Rev Recd Date: Oct. 16, 2020
Available Online: Jan. 24, 2022
Publish Date: Aug. 15, 2021

Abstract

Abstract

Surface enhanced Raman spectroscopy (SERS) and confocal Raman microscopy are applied to investigate the structure and the molecular arrangement of sub-micron furosemide and polyvinylpyrrolidone (furosemide/PVP) particles produced by spray flash evaporation (SFE). Morphology, size and crystallinity of furosemide/PVP particles are analyzed by scanning electron microscopy (SEM) and X-ray powder diffraction (XRPD). Far-field Raman spectra and confocal far-field Raman maps of furosemide/PVP particles are interpreted based on the far-field Raman spectra of pure furosemide and PVP precursors. Confocal far-field Raman microscopy shows that furosemide/PVP particles feature an intermixture of furosemide and PVP molecules at the sub-micron scale. SERS and surface-enhanced confocal Raman microscopy (SECoRM) are performed on furosemide, PVP and furosemide/PVP composite particles sputtered with silver (40 nm). SERS and SECoRM maps reveal that furosemide/PVP particle surfaces mainly consist of PVP molecules. The combination of surface and bulk sensitive analyses reveal that furosemide/PVP sub-micron particles are formed by the agglomeration of primary furosemide nano-crystals embedded in a thin PVP matrix. Interestingly, both far-field Raman microscopy and SECoRM provide molecular information on a statistically-relevant amount of sub-micron particles in a single microscopic map; this combination is thus an effective and time-saving tool for investigating organic sub-micron composites.
- SERS,
- Confocal Raman microscopy,
- Surface characterization,
- Sub-micron particles,
- Pharmaceutic composites

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References(46)

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