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Rivaroxaban polymeric amorphous solid dispersions: Moisture-induced thermodynamic phase behavior and intermolecular
Afroditi Kapourani1, Elisavet Vardaka1, Konstantinos Katopodis1
1Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Summary
This study uses thermodynamic modeling and molecular simulations to assess the physical stability of Rivaroxaban amorphous solid dispersions (ASDs). Flory-Huggins modeling accurately predicted ASD stability, highlighting moisture interaction as key to physical stability.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Computational Chemistry
Background:
- Amorphous solid dispersions (ASDs) enhance drug solubility and bioavailability.
- Predicting the physical stability of ASDs, especially under varying humidity, is crucial for drug formulation.
- Rivaroxaban (RXB) is a widely used anticoagulant, and its ASD stability is of significant interest.
Purpose of the Study:
- To evaluate the physical stability and intermolecular interactions of Rivaroxaban ASDs in different polymeric carriers.
- To utilize thermodynamic modeling and molecular simulations to predict and understand ASD stability.
- To compare the predictive power of Flory-Huggins modeling with experimental observations.
Main Methods:
- Flory-Huggins (FH) lattice solution theory was used for thermodynamic modeling and phase diagram construction.
- ASD samples were stored under various relative humidity (RH) conditions (0%, 60%, 75%) for up to six months.
- Experimental verification involved polarized light microscopy, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR).
- Molecular dynamics (MD) simulations were employed to interpret stability differences.
Main Results:
- FH modeling showed good agreement with experimental results, identifying coPVP and PVP as less stable carriers compared to SOL and HPMCAS.
- The study confirmed that moisture interaction plays a more critical role in ASD physical stability than intermolecular interactions between ASD components.
- MD simulations indicated similar intermolecular interactions across all tested ASDs.
Conclusions:
- Flory-Huggins based modeling is a valuable tool for predicting the long-term physical stability of ASDs under high humidity.
- Polymer selection significantly impacts the physical stability of Rivaroxaban ASDs.
- Understanding moisture-drug-polymer interactions is essential for developing stable amorphous solid dispersions.
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