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Related Concept Videos

Raman Spectroscopy: Overview01:20

Raman Spectroscopy: Overview

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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.
However, a small fraction of the scattered light exhibits a frequency shift due to the exchange of energy between the incident photons and...
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Raman Spectroscopy Instrumentation: Overview01:26

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A conventional Raman spectrophotometer includes a laser source, a sample holding system, a wavelength selector, and a detector.
The monochromatic laser source, typically using visible or near-infrared radiation, generates a highly focused beam of light. This light interacts with the molecules of the sample, scattering some of the light. Liquid and gaseous samples are usually tested in ordinary glass capillaries, while solids can be analyzed as powders packed in capillaries or as potassium...
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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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Updated: Jun 8, 2025

Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging
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Insights into pharmaceutical co-crystallization using coherent Raman microscopy.

Alba M Arbiol Enguita1, Elina Harju1, Lea Wurr1

  • 1Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00790 Helsinki, Finland.

Journal of Pharmaceutical Sciences
|November 4, 2024
PubMed
Summary
This summary is machine-generated.

Coherent Raman microscopy, including CARS and SRS, effectively visualizes and quantifies active pharmaceutical ingredient (API) co-crystal formation during liquid-assisted ball milling, revealing previously undetected forms and process dynamics.

Keywords:
Analytical chemistryCo-crystal(s)Imaging method(s)Materials scienceMillingPhase transformation(s)Poorly water-soluble drug(s)Raman spectroscopySolid-stateSpectroscopy

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Area of Science:

  • Pharmaceutical Sciences
  • Chemical Engineering
  • Materials Science

Background:

  • Co-crystallization is crucial for formulating active pharmaceutical ingredients (APIs).
  • Understanding co-crystallization behavior under various process conditions is essential for successful formulation.
  • Established analytical methods may not fully capture the complex dynamics of co-crystallization.

Purpose of the Study:

  • To investigate the application of coherent Raman microscopy techniques for studying co-crystallization.
  • To compare narrowband coherent anti-Stokes Raman scattering (CARS) and hyperspectral stimulated Raman scattering (SRS) for co-crystallization analysis.
  • To evaluate the ability of these techniques to provide qualitative and quantitative insights into the co-crystallization process.

Main Methods:

  • Liquid-assisted ball milling was used to induce co-crystallization of indomethacin and nicotinamide.
  • Narrowband CARS microscopy with univariate peak position analysis was employed.
  • Hyperspectral SRS imaging combined with classical least squares multivariate analysis was utilized.
  • Results were compared with conventional solid-state analysis methods.

Main Results:

  • Narrowband CARS visualized co-crystal formation but faced challenges with component identification due to signal mixing.
  • Hyperspectral SRS imaging provided confident separation of components, proving robust for qualitative and quantitative co-crystallization imaging.
  • Coherent Raman imaging explained divergent endpoints from conventional methods and detected trace forms.
  • The study demonstrated the influence of ethanol content on co-crystal formation reversal during milling.

Conclusions:

  • Coherent Raman microscopy, particularly SRS, is a valuable tool for analyzing co-crystallization processes.
  • These techniques offer enhanced insights into co-crystal formation, including the detection of trace components and process dynamics.
  • The findings highlight the added value of coherent Raman microscopy for pharmaceutical formulation development.