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 par-ticles 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.