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Raman Spectroscopy: Overview01:20

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The underlying principle of Raman spectroscopy is based on the interaction between light and matter, specifically molecules' inelastic scattering of photons. When a monochromatic beam of light, typically from a laser source, interacts with a sample, most scattered light has the same frequency as the incident light. This is known as Rayleigh scattering.
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X-ray Diffraction of Biological Samples01:10

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X-ray diffraction or XRD is an analytical tool that utilizes X-rays to study ordered structures such as crystalline organic and inorganic samples, polycrystalline materials, proteins, carbohydrates, and drugs.
According to Bragg's law, when X-rays strike the sample positioned on a stage, the rays are  scattered by the electron clouds around the sample atoms. The  X-ray diffraction or scattering is caused by constructive interference of the X-ray waves that reflect off the internal...
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Related Experiment Video

Updated: Jun 7, 2025

Methods of Ex Situ and In Situ Investigations of Structural Transformations: The Case of Crystallization of Metallic Glasses
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Dynamic Phase Behavior of Amorphous Solid Dispersions Revealed with In Situ Stimulated Raman Scattering Microscopy.

Teemu Tomberg1, Ilona Hämäläinen1,2, Clare J Strachan1

  • 1Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00790, Finland.

Molecular Pharmaceutics
|November 19, 2024
PubMed
Summary

Stimulated Raman scattering (SRS) microscopy visualizes real-time chemical changes in amorphous solid dispersions (ASDs) during dissolution. This technique offers crucial insights for developing effective ASD formulations.

Keywords:
amorphous solid dispersionamorphous−amorphous phase separationdissolutionimagingpoorly solublestimulated Raman scattering microscopy

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Area of Science:

  • Pharmaceutical Sciences
  • Materials Science
  • Chemical Imaging

Background:

  • Amorphous solid dispersions (ASDs) are crucial for improving drug solubility and bioavailability.
  • Understanding the dynamic phase behavior of ASDs upon contact with dissolution media is vital for formulation development.
  • Current imaging techniques often lack the necessary chemical specificity and temporal resolution to capture these dynamic processes.

Purpose of the Study:

  • To apply in situ stimulated Raman scattering (SRS) microscopy for real-time, chemically specific imaging of dynamic phase phenomena in ASDs.
  • To quantitatively analyze the behavior of ASDs, including drug, polymer, and water distribution, during dissolution.
  • To provide insights into water-induced phase transitions and drug release mechanisms within ASDs.

Main Methods:

  • Utilized in situ SRS microscopy with fast spectral focusing for dynamic imaging.
  • Employed multivariate unmixing of SRS spectra for semi-quantitative analysis of component distribution.
  • Integrated correlative sum frequency generation and confocal reflection microscopy for enhanced phase and crystallinity sensitivity.

Main Results:

  • Real-time imaging revealed water penetration, surface-directed, and bulk phase separation in ASDs with varying drug loadings (20-60% w/w).
  • Drug loading and phase-dependent drug and polymer release behaviors were quantitatively visualized.
  • Liquid-liquid phase separation was observed in ASDs with 20% drug loading.

Conclusions:

  • SRS microscopy with fast spectral focusing provides high-resolution, quantitative insights into water-induced phase phenomena in ASDs.
  • The technique enables simultaneous chemical, solid-state, temporal, and spatial resolution of dynamic processes.
  • These findings are critical for optimizing ASD formulation design and predicting drug release performance.