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

• Main Authors: Busby, Y. (Author), Coty, J.-B (Author), Hübner, J. (Author), Spitzer, D. (Author)
• Format: Article
• Language: English
• Published: Xi'an Jiaotong University 2021
• Subjects: aerosol; Article; confocal microscopy; Confocal Raman microscopy; controlled study; crystal structure; evaporation; furosemide; microscopy; nanocrystal; particle size; Pharmaceutic composites; povidone; Raman spectrometry; scanning electron microscopy; SERS; silver; Sub-micron particles; Surface characterization; surface enhanced Raman spectroscopy; surface property; X ray powder diffraction
• Online Access: View Fulltext in Publisher

 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. © 2020 Xi'an Jiaotong University