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

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.

Formation mechanisms of sub-micron pharmaceutical composite particles derived from far-and near-field Raman microscopy / 药物分析学报

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.

Surface characterization of nanoscale co-crystals enabled through tip enhanced Raman spectroscopy.

Atomic Force Microscopy coupled with Tip Enhanced Raman Spectroscopy (AFM-TERS) was applied to obtain information about the structure and surface composition of single nano co-crystals. For this purpose, a co-crystalline system consisting of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazatetracyclo-[5.5.0.03,11.05,9]-dodecane (CL-20) and 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX) in a molar ratio of 2 : 1 (CL-20/HMX) was chosen. CL-20/HMX nano-plates were prepared by spray flash evaporation. To ensure co-crystallinity and nanostructures, powder X-ray diffraction and AFM investigations were performed. The results demonstrate that coherence lengths and particle dimensions are on a similar level though coherence lengths appear shorter than measured particle dimensions. According to this fact, defects inside the nano co-crystals are minimized. The co-crystallinity was additionally proven by confocal Raman spectroscopy. Here, marker bands for pristine CL-20 and HMX were chosen which appear in the CL-20/HMX spectrum in an intensity ratio of ∼2.5 : 1 (CL-20 : HMX). Afterwards surface investigations of single CL-20/HMX nano-plates were performed by AFM-TERS. Due to the surface sensitivity of TERS, these experiments reveal that the ratio of the Raman intensities between CL-20 and HMX inverts at CL-20/HMX nano-plate surfaces. Therefore, it is concluded that nano co-crystal surfaces consist of molecular layers of HMX. A theoretical approximation of the normal coordinates of the investigated marker vibrations supports this conclusion since it can exclude the occurrence of the intensity ratio inversion because of the given orientation between CL-20/HMX nano-plates and the Raman scattering system. Based on this finding, an impact ignition mechanism is proposed, enabling explanation of the close impact sensitivity values of ß-HMX and CL-20/HMX.

Surface Functionalization and Electrical Discharge Sensitivity of Passivated Al Nanoparticles.

Passivated aluminum nanoparticles are surface functionalized to elucidate their sensitivity against an electrical discharge. Two size fractions that differ in surface morphology are investigated. Electronic interactions between the partly inert, partly energetic organic molecules used for surface functionalization and the alumina surface are analyzed in detail. The nanoparticle surfaces are modified with the well-established, inert 2-[2-(2-methoxyethoxy)ethoxy]acetic acid, whereas energetic surface modification is achieved using 1,3,5-trinitroperhydro-1,3,5-triazine or the acidic and aromatic 2,4,6-trinitrophenol. A mechanistic model for the chemical surface functionalization of Al nanoparticles is hypothesized and corroborated by comprehensive optical and Fourier transform infrared spectroscopy studies. The surface structures are adjusted by developing a tunable stabilization procedure that prevents sedimentation and hence increases the saturation concentration in the liquid phase and finally affects the sensitivity character in view of electrical discharge ignition of dry powders. Detailed material characterization is conducted using transmission electron microscopy, combined with energy-dispersive X-ray spectroscopy and various absorption spectroscopy techniques (steady state in the infrared and ultraviolet/visible regime). The adjustment of surface structures of the distinct Al nanoparticle samples offers a valuable tool for tuning and tailoring the reactivity, sensitivity, stability, and energetic performances of the nanoparticles, and thereby enables the safe use of these multipurpose nanoparticles.