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Solid-Liquid Equilibrium in Co-Amorphous Systems: Experiment and Prediction
Alžběta Zemánková1, Fatima Hassouna2, Martin Klajmon1
1Department of Physical Chemistry, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague, Czech Republic.
Molecules (Basel, Switzerland)
|March 29, 2023
Summary
This study investigated solid-liquid equilibrium for four active pharmaceutical ingredient (API) binary systems, forming co-amorphous systems (CAMs). Experimental data and theoretical models were used to evaluate phase diagrams and determine accurate glass transition temperatures for naproxen.
Area of Science:
- Pharmaceutical Science
- Physical Chemistry
- Materials Science
Background:
- Co-amorphous systems (CAMs) are crucial for improving the solubility and bioavailability of poorly soluble active pharmaceutical ingredients (APIs).
- Understanding the solid-liquid equilibrium (SLE) phase diagrams of API binary mixtures is essential for designing stable CAMs.
- Accurate determination of the glass transition temperature (Tg) is vital for predicting the physical stability of amorphous pharmaceutical systems.
Purpose of the Study:
- To experimentally investigate the solid-liquid equilibrium (SLE) of four binary systems composed of APIs capable of forming co-amorphous systems (CAMs).
- To evaluate the predictive capabilities of the perturbed-chain statistical associating fluid theory (PC-SAFT) and conductor-like screening model for real solvents (COSMO-RS) for API-API binary systems.
- To accurately determine the glass transition temperature (Tg) of naproxen by stabilizing its amorphous form within binary mixtures.
Main Methods:
- Experimental determination of SLE using differential scanning calorimetry (DSC) for naproxen-indomethacin, naproxen-ibuprofen, naproxen-probucol, and indomethacin-paracetamol binary systems.
- Thermodynamic modeling using the PC-SAFT equation of state and COSMO-RS (via Amsterdam Modeling Suite) to predict liquidus and eutectic temperatures.
- Measurement and modeling of Tg for binary mixtures to stabilize amorphous naproxen and identify erroneous literature values.
Main Results:
- All investigated binary mixtures formed eutectic systems, with CAMs successfully formed upon melting and quenching for most compositions.
- Comparison between experimental SLE data and theoretical predictions from PC-SAFT and COSMO-RS revealed the models' ability to predict phase diagrams for API-API systems.
- A new, reliable Tg value for naproxen was determined, and discrepancies in existing literature values were identified.
Conclusions:
- The study successfully characterized the SLE and CAM formation for four API binary systems, providing valuable data for formulation development.
- PC-SAFT and COSMO-RS show potential for predicting phase behavior in API-API binary systems, aiding in the rational design of co-amorphous formulations.
- The accurate determination of naproxen's Tg enhances the understanding of its recrystallization tendency and improves the prediction of amorphous solid stability.
Keywords:
COSMO-RSPC-SAFTactive pharmaceutical ingredientsco-amorphous systemsglass transition temperaturephase diagramsphysical stabilitysolid–liquid equilibriumMore Related Videos
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