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(SECo RM) are performed on furosemide, PVP and furosemide/PVP composite particles sputtered with silver(40 nm). SERS and SECo RM 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 nanocrystals embedded in a thin PVP matrix. Interestingly, both far-field Raman microscopy and SECo RM 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.

COHERENT ANTI-STOKES RAMAN SCATTERING MICROSCOPY TO MONITOR DRUG DISSOLUTION IN DIFFERENT ORAL PHARMACEUTICAL TABLETS

Coherent anti-Stokes Raman scattering(CARS)microscopy is used to visualize the release of a model drug(theophylline)from a lipid(tripalmitin)based tablet during dissolution.The effects of transformation and dissolution of the drug are imaged in real time.This study reveals that the manufacturing process causes significant differences in the release process:tablets prepared from powder show formation of theophylline monohydrate on the surface which prevents a controlled drug release,whereas solid lipid extrudates did not show formation of monohydrate.This visualization technique can aid future tablet design.

Photodetection-induced relative timing jitter in synchronized time-lens source for coherent Raman scattering microscopy

Synchronized time lens source is a novel method to generate synchronized optical pulses to mode-locked lasers,and has found widespread applications in coberent Raman scattering microscopy.Relative timing jitter between the mode-locked laser and the synchronized time-lens source is a key parameter for evaluating the synchronization peformance of such synchronized laser sys-tems.However,the origins of the relative timing jitter in such systens are not fully determined,which in turn prevents the experimental efforts to optimize the synchronization perfornance.Here,we demonstrate,through theoretical modeling and mumerical simulation,that the photo-detction could be one physical origin of the relative timing jitter.Comparison with relative timing jitter due to the intrinsic timing jitter of the mode-locked laser is also demonstrated,revealing different qualitative and quantitative behavios.Based on the nature of this photo-detection-induced timing jitter,we further propose several strategies to reduce the relative timing jitter.Our thoretical results will provide guidelines for optimizing synchronization performance in experiments.

Nonlinear optical microscopy for skin in vivo:Basics,development and applications

Multi-photon microscopy(MPM)and coherent anti-Stokes Raman scattering(CARS)are two advanced nonlinear optical imaging techniques,which provide complementary information and have great potential in combination for noninvasive in vrito biomedical applications.This paper provides a detailed discussion of the basics,development and applications of these technologies for in vrivo skin research,covering the following topics:The principle and advantage of MPM and CARS,instrumentation development for in vino applications,MPM and CARS of normal skin,application of MPM and CARS in skin cancer and disease diagnosis;application of MPM in skin disease intervention,ie.,imaging guided two-photon photothermolysis.

Coherent Raman scattering imaging of lipid metabolism in cancer

Cancer cells dysregulate lipid metabolism to accelerate energy production and biomolecule synthesis for rapid growth.Lipid metabolism is highly dynamic and intrinsically heterogeneous at the single cell level.Although°uorescence microscopy has been commonly used for cancer research,bulky°uorescent probes can hardly label small lipid molecules without perturbing their biological activities.Such a challenge can be overcome by coherent Raman scattering(CRS)microscopy,which is capable of chemically selective,highly sensitive,submicron resolution and high-speed imaging of lipid molecules in single live cells without any labeling.Recently developed hyperspectral and multiplex CRS microscopy enables quantitative mapping of various lipid metabolites in situ.Further incorporation of CRS microscopy with Raman tags greatly increases molecular selectivity based on the distinct Raman peaks well separated from the endogenous cellular background.Owing to these unique advantages,CRS microscopy sheds new insights into the role of lipid metabolism in cancer development and progression.This review focuses on the latest applications of CRS microscopy in the study of lipid metabolism in cancer.

Effects of Different Concentrations and Exposure Time of Sodium Hypochlorite on the Structural,Compositional and Mechanical Properties of Human Dentin

This study evaluated the effects of sodium hypochlorite（NaOCl） with different concentrations and exposure time on the structural, compositional and mechanical properties of human dentin in vitro. Sixty dentin slabs were obtained from freshly extracted premolars, randomly distributed into four groups（n=15）, and treated with 1%, 5%, 10% NaOCl and distilled water（control group）, respectively, for a total of 60 min. Attenuated total reflection infrared（ATR-IR） spectroscopy, Raman spectroscopy and X-ray diffraction（XRD） were carried out before, 10 min and 60 min after the treatment. Scanning electron microscopy（SEM） and flexural strength test were conducted as well. The results showed that dentins experienced morphological alterations in the NaOCl groups, but not in the control group. Two-way repeated-measures analysis of variance revealed that the carbonate：mineral ratio（C：M）, Raman relative intensity（RRI）, a-axis, c-axis length and full width at half maximum（FWHM） with the increase of time and concentration in the NaOCl groups were not significantly different from those in the control group（P〉0.05）. Nevertheless, the mineral：matrix ratio（M：M） increased and the flexural strength declined with the increase of concentration and the extension of time in the NaOCl groups（P〈0.05）. Additionally, it was found that the M：M and the flexural strength remained unchanged after 1% NaOCl treatment（P〉0.05）, and the morphology changes were unnoticeable within 10 min in 1% NaOCl group. These results indicated that NaOCl has no significant effects on the inorganic mineral of human dentin; but it undermines and eliminates the organic content concentration-and time-dependently, which in turn influences the flexural strength and toughness of dentins. In addition, an irrigation of 1% NaOCl within 10 min can minimize the effects of NaOCl on the structural and mechanical properties of dentin during root canal treatment.

Thermal plasma synthesis of SiC

Synthesis of silicon carbide has been carried out using thermal plasma processing technique using SiO2 as the solid feed and CH4 as the gaseous reducing agent. Thermochemical calculations have been performed varying the molar ratio of silicon dioxide and methane to determine the feasibility of the reaction. Experiments using a molar ratio of SiO2：CH4 equal to 1：2 produced maximum yield of SiC of about 65 mol % at a solid feed rate of 5 g/min. Mostly spherical morphology with some nanorods has been observed. The presence of Si had been observed and was quantified using XRD, HRTEM, Raman spectroscopy and X-ray photoelectron microscopy （XPS）. Si acts as a nucleating agent for SiC nanorods to grow.