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Coherent anti-Stokes Raman Scattering CARS Microscopy Visualizes Pharmaceutical Tablets During Dissolution
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A comparative study of applying backscattering and transmission Raman spectroscopy to quantify solid-state form
Haichen Nie1, Gerard Klinzing2, Wei Xu2
1Center for Materials Science and Engineering, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States.
International Journal of Pharmaceutics
|February 24, 2022
Summary
This study compares Raman spectroscopy methods for quantifying solid form changes in tablets. Combining backscattering and transmission Raman effectively captures both local and bulk chemical information for accurate analysis.
Area of Science:
- Pharmaceutical Sciences
- Analytical Chemistry
- Materials Science
Background:
- Accurate quantification of solid form conversions is crucial for pharmaceutical processing and storage.
- Raman spectroscopy offers potential for non-destructive analysis of solid-state changes.
Observation:
- Transmission Raman spectroscopy provides bulk information but can miss localized changes due to signal attenuation.
- Backscattering Raman spectroscopy, with subsampling, can detect low-level, spatially distributed form conversions on tablet surfaces.
- Uneven shear stress during tablet compression leads to variations in solid form conversion between tablet edges and centers.
Findings:
- This study comparatively evaluates backscattering and transmission Raman spectroscopy for quantifying salt disproportionation in tablet matrices.
- Different spectral processing approaches and calibration models were assessed for quantitative analysis.
- Combined use of focused backscattering and transmission Raman spectrometry provides complementary local and bulk chemical information.
Implications:
- Integrating both backscattering and transmission Raman spectroscopy offers a more complete understanding of solid form conversions in tablets.
- This combined approach enhances the ability to detect and quantify subtle, spatially heterogeneous changes within pharmaceutical formulations.
- Optimized Raman measurement and data processing strategies are key for effective solid form analysis in pharmaceutical development and quality control.
Keywords:
ChemometricsPartial Least Square modelPhysical stabilityProcess induced phase transitionsRaman spectrometrySalt disproportionationMore Related Videos
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