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Updated: Aug 28, 2025
06:54
Author Spotlight: Advances in Nanoscale Infrared Spectroscopy to Explore Multiphase Polymeric Systems
Published on: June 23, 2023
904
Detecting different amorphous - Amorphous phase separation patterns in co-amorphous mixtures with high resolution
Tuomas Kilpeläinen1, Tuomas Ervasti1, Emilia Uurasjärvi2
1School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
Summary
Amorphous solid dispersions improve drug solubility but can phase separate. This study uses imaging FTIR spectroscopy to visualize and quantify amorphous-amorphous phase separation in drug mixtures, revealing distinct patterns of separation over time.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Spectroscopy
Background:
- Many active pharmaceutical ingredients (APIs) exhibit poor aqueous solubility, limiting their therapeutic efficacy.
- Amorphous forms of APIs offer enhanced solubility but are thermodynamically unstable, prone to crystallization.
- Phase separation in co-amorphous systems precedes crystallization, making its study crucial for formulation stability.
Purpose of the Study:
- To develop and validate a high-resolution imaging method for studying amorphous-amorphous phase separation.
- To investigate the kinetics and patterns of phase separation in API-API binary mixtures.
- To assess the reproducibility and reliability of imaging Fourier transform infrared (FTIR) spectroscopy for this application.
Main Methods:
- Amorphization of seven API-API binary mixtures (1:1 M ratio) via melt-quenching.
- Thermodynamic characterization using differential scanning calorimetry (DSC) to determine glass transition temperature (Tg) and melting point (Tm).
- High-resolution imaging FTIR spectroscopy in transmission mode to monitor phase separation above Tg, analyzed with principal component analysis (PCA).
Main Results:
- Imaging FTIR spectroscopy demonstrated reproducible detection of amorphous-amorphous phase separation.
- Phase separation kinetics were visualized using scatter-plots of phase-separated pixels.
- Separation patterns were observed as either sigmoidal or linear, dependent on the specific API mixture.
Conclusions:
- Imaging FTIR spectroscopy is a viable technique for studying amorphous-amorphous phase separation in pharmaceutical systems.
- The method provides insights into the stability and physical transformations of amorphous drug formulations.
- Understanding phase separation is critical for designing stable and effective amorphous solid dispersions.
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