Abstract
Purpose
To study the impact of different surfactants on the supersaturation of nifedipine stabilized with HPMC and PVP-VA.
Methods
Different kinds of surfactants, including one cationic surfactant, two anionic surfactants, and three nonionic surfactants, were used to evaluate their impacts on the supersaturation of nifedipine stabilized with HPMC and PVP-VA. Polymer-surfactant interaction was studied by nuclear magnetic resonance (NMR) and fluorescent method. Solubility of nifedipine in solutions containing different amounts of polymers and surfactants was measured. Drug-polymer affinity was evaluated by measuring the percentage of polymer coprecipitated together with the drug from supersaturated solutions.
Results
Different polymer-surfactant combinations had different impacts on the supersaturation of nifedipine. Some combinations, such as PVP-VA/SLS and PVP-VA/NaTC under higher surfactant concentrations, showed improved drug supersaturation, due to increased drug solubility or polymer-surfactant synergy; while other combinations, such as HPMC/SLS and HPMC/Tween 20 under lower surfactant concentrations, showed reduced drug supersaturation, which could result from competitive surfactant-polymer or drug-surfactant interaction that disrupted pre-existent drug-polymer interaction.
Conclusions
The ultimate impacts of various surfactants on polymer stabilized nifedipine supersaturation could be attributed to the interplay between different factors, including solubility enhancement of the drug, drug-polymer-surfactant interactions, and polymer-surfactant synergy.
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Abbreviations
- AUC:
-
Area under the curve
- CAC:
-
Critical aggregation concentration CMC
Critical micelle concentration DMSO
Dimethylsulfoxide
- DTAB:
-
Dodecyl trimethyl ammonium bromide
- ELSD:
-
Evaporative light scattering detector
- GI:
-
Gastrointestinal
- HPLC:
-
High performance liquid chromatography
- HPMC:
-
Hydroxypropyl methylcellulose
- NaTC:
-
Sodium taurocholate
- NMR:
-
Nuclear magnetic resonance
- PBS:
-
Phosphatic buffer solution
- PCP:
-
Polymer coprecipitation percentage
- PVP-VA:
-
Polyvinylpyrrolidone-co-vinyl-acetate
- PXRD:
-
Powder x-ray diffraction
- SDDS:
-
Supersaturating drug delivery systems
- SLS:
-
Sodium lauryl sulfate
- SP:
-
Supersaturation parameter
- TPGS:
-
D-α-Tocopherol polyethylene glycol succinate
- UV:
-
Ultraviolet
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Acknowledgments
This research is supported by China National Nature Science Foundation (Project Number 81573355), and by Janssen Pharmaceuticals, Inc., a pharmaceutical company of Johnson & Johnson.
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Wang, S., Liu, C., Chen, H. et al. Impact of Surfactants on Polymer Maintained Nifedipine Supersaturation in Aqueous Solution. Pharm Res 37, 113 (2020). https://doi.org/10.1007/s11095-020-02837-5
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DOI: https://doi.org/10.1007/s11095-020-02837-5