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Prediction of Successful Amorphous Solid Dispersion Pairs through Liquid State Nuclear Magnetic Resonance
Ana L Coutinho1, Kellie Hom1, James E Polli1
1Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, United States.
Molecular Pharmaceutics
|November 1, 2024
Summary
Nuclear magnetic resonance (NMR) can predict polymer suitability for amorphous solid dispersions (ASDs). Strong drug-polymer interactions identified by NMR correlate with prolonged drug supersaturation and reduced precipitation, streamlining ASD development.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Analytical Chemistry
Background:
- Amorphous solid dispersions (ASDs) enhance drug solubility and bioavailability.
- The
- parachute effect
- in ASDs relies on polymer-mediated drug supersaturation.
- Understanding drug-polymer interactions is crucial for ASD formulation.
Purpose of the Study:
- To evaluate liquid state nuclear magnetic resonance (NMR) as a tool for polymer selection in ASD development.
- To correlate NMR-detected drug-polymer interactions with drug precipitation kinetics in supersaturation studies.
- To streamline the process of identifying suitable polymers for ASDs.
Main Methods:
- Drug-polymer interactions were assessed using saturation transfer difference NMR (STD-NMR), T1 relaxation time, and 2D-1H NOESY experiments.
- Supersaturation studies were conducted using the solvent-shift methodology to measure precipitation inhibition.
- 1H NMR findings were compared with experimental supersaturation data for etravirine with HPMC, HPMCAS-M, and PVP-VA.
Main Results:
- STD-NMR and T1 relaxation time indicated preferential binding of etravirine to HPMCAS-M > HPMC ≫ PVP-VA.
- NMR data provided insights into specific drug-polymer binding sites.
- HPMC and HPMCAS-M demonstrated strong interactions, effectively inhibiting etravirine precipitation and maintaining supersaturation, unlike PVP-VA.
- Supersaturation studies confirmed that HPMC and HPMCAS-M prolonged etravirine dissolution compared to PVP-VA.
Conclusions:
- Liquid state 1H NMR is a promising, non-destructive method for predicting polymer performance in ASDs.
- Strong drug-polymer interactions detected by NMR correlate with enhanced drug supersaturation and reduced precipitation.
- NMR can significantly streamline polymer selection for ASD development, saving time and resources.
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