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PreprintCC BY-NCChemRxiv

Analysis of the pH-Dependent Phase Behavior of Amorphous Solid Dispersions Using in situ Stimulated Raman Scattering Microscopy

  • Aino Majanen1,2
  • Clare Strachan1,2
  • Teemu Tomberg1,2,3
  1. 1Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy
  2. 2University of Helsinki
  3. 3Department of Chemistry, Faculty of Science
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Abstract

In this study, in situ stimulated Raman scattering (SRS) microscopy was employed as a novel analytical method to investigate the pH-dependent phase behavior of amorphous solid dispersions (ASDs) during hydration. Ibuprofen–poly(1-vinylpyrrolidone-co-vinyl acetate) (IBU-PVPVA) ASDS were used as model systems. The ASDs underwent multiple structural changes including polymer swelling, gel-layer formation and phase separation. To monitor these processes, binary IBU-PVPVA ASDs with six drug loadings were studied under four pH conditions using in situ hyperspectral stimulated Raman scattering (SRS) microscopy with spectral focusing, further augmented with correlative confocal reflection imaging. Spectral imaging data analysis was performed with classical least squares, preceded by multivariate curve resolution-alternating least squares estimation. Supportive solid-state analysis was performed using modulated temperature differential scanning calorimetry, polarized light microscopy, thermogravimetric analysis, and spontaneous Raman spectroscopy combined with principal component analysis. The results show that in situ SRS microscopy enables detailed real-time visualization of pH-dependent structural evolution in ASDs during hydration. The phase behavior was found to be affected by the environmental pH and buffering conditions, expected to ultimately determine drug release performance.

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Cite

BibTeXRIS
BibTeX
@misc{majanen2026analysis,
  title = {{Analysis of the pH-Dependent Phase Behavior of Amorphous Solid Dispersions Using in situ Stimulated Raman Scattering Microscopy}},
  author = {Aino Majanen and Clare Strachan and Teemu Tomberg},
  howpublished = {ChemRxiv},
  year = {2026},
  month = oct,
  doi = {10.26434/chemrxiv.15010061/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010061/v1},
  note = {CC BY-NC},
}
RIS
TY  - UNPB
TI  - Analysis of the pH-Dependent Phase Behavior of Amorphous Solid Dispersions Using in situ Stimulated Raman Scattering Microscopy
AU  - Aino Majanen
AU  - Clare Strachan
AU  - Teemu Tomberg
PY  - 2026
DA  - 2026/10/07
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15010061/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010061/v1
AB  - In this study, in situ stimulated Raman scattering (SRS) microscopy was employed as a novel analytical method to investigate the pH-dependent phase behavior of amorphous solid dispersions (ASDs) during hydration. Ibuprofen–poly(1-vinylpyrrolidone-co-vinyl acetate) (IBU-PVPVA) ASDS were used as model systems. The ASDs underwent multiple structural changes including polymer swelling, gel-layer formation and phase separation. To monitor these processes, binary IBU-PVPVA ASDs with six drug loadings were studied under four pH conditions using in situ hyperspectral stimulated Raman scattering (SRS) microscopy with spectral focusing, further augmented with correlative confocal reflection imaging. Spectral imaging data analysis was performed with classical least squares, preceded by multivariate curve resolution-alternating least squares estimation. Supportive solid-state analysis was performed using modulated temperature differential scanning calorimetry, polarized light microscopy, thermogravimetric analysis, and spontaneous Raman spectroscopy combined with principal component analysis. The results show that in situ SRS microscopy enables detailed real-time visualization of pH-dependent structural evolution in ASDs during hydration. The phase behavior was found to be affected by the environmental pH and buffering conditions, expected to ultimately determine drug release performance.
ER  -