Comparative analysis of drug-salt-polymer interactions by experiment and molecular simulation improves biopharmaceutical performance
The propensity of poorly water-soluble drugs to aggregate at supersaturation impedes their bioavailability. Supersaturated amorphous drug-salt-polymer systems provide an emergent approach to this problem. However, the effects of polymers on drug-drug interactions in aqueous phase are largely unexplo...
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
25 September 2023
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| In: |
Communications chemistry
Year: 2023, Jahrgang: 6, Pages: 1-18 |
| ISSN: | 2399-3669 |
| DOI: | 10.1038/s42004-023-01006-0 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s42004-023-01006-0 Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s42004-023-01006-0 
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| Verfasserangaben: | Sumit Mukesh, Goutam Mukherjee, Ridhima Singh, Nathan Steenbuck, Carolina Demidova, Prachi Joshi, Abhay T. Sangamwar & Rebecca C. Wade |
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| 245 | 1 | 0 | |a Comparative analysis of drug-salt-polymer interactions by experiment and molecular simulation improves biopharmaceutical performance |c Sumit Mukesh, Goutam Mukherjee, Ridhima Singh, Nathan Steenbuck, Carolina Demidova, Prachi Joshi, Abhay T. Sangamwar & Rebecca C. Wade |
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| 520 | |a The propensity of poorly water-soluble drugs to aggregate at supersaturation impedes their bioavailability. Supersaturated amorphous drug-salt-polymer systems provide an emergent approach to this problem. However, the effects of polymers on drug-drug interactions in aqueous phase are largely unexplored and it is unclear how to choose an optimal salt-polymer combination for a particular drug. Here, we describe a comparative experimental and computational characterization of amorphous solid dispersions containing the drug celecoxib, and a polymer, polyvinylpyrrolidone vinyl acetate (PVP-VA) or hydroxypropyl methylcellulose acetate succinate, with or without Na+/K+ salts. Classical models for drug-polymer interactions fail to identify the best drug-salt-polymer combination. In contrast, more stable drug-polymer interaction energies computed from molecular dynamics simulations correlate with prolonged stability of supersaturated amorphous drug-salt-polymer systems, along with better dissolution and pharmacokinetic profiles. The celecoxib-salt-PVP-VA formulations exhibit excellent biopharmaceutical performance, offering the prospect of a low-dosage regimen for this widely used anti-inflammatory, thereby increasing cost-effectiveness, and reducing side-effects. | ||
| 650 | 4 | |a Atomistic models | |
| 650 | 4 | |a Drug delivery | |
| 650 | 4 | |a Pharmaceutics | |
| 650 | 4 | |a Polymers | |
| 700 | 1 | |a Mukherjee, Goutam |e VerfasserIn |4 aut | |
| 700 | 1 | |a Singh, Ridhima |e VerfasserIn |4 aut | |
| 700 | 1 | |a Steenbuck, Nathan |e VerfasserIn |0 (DE-588)1332725597 |0 (DE-627)1891116800 |4 aut | |
| 700 | 1 | |a Demidova, Carolina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Joshi, Prachi |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sangamwar, Abhay T. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wade, Rebecca C. |e VerfasserIn |0 (DE-588)102801774X |0 (DE-627)730136000 |0 (DE-576)276591402 |4 aut | |
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