A study of hydrophobic domain formation of polymeric drug precipitation inhibitors in aqueous solution
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Author (Corporation)
Publication date
01.07.2024
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Type
01A - Journal article
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Parent work
European Journal of Pharmaceutical Sciences
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DOI of the original publication
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Series
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Volume
198
Issue / Number
Pages / Duration
106791
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Publisher / Publishing institution
Elsevier
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Abstract
Despite the widespread use of polymers as precipitation inhibitors in supersaturating drug formulations, the current understanding of their mechanisms of action is still incomplete. Specifically, the role of hydrophobic drug interactions with polymers by considering possible supramolecular conformations in aqueous dispersion is an interesting topic. Accordingly, this study investigated the tendency of polymers to create hydrophobic domains, where lipophilic compounds may nest to support drug solubilisation and supersaturation. Fluorescence spectroscopy with the environment-sensitive probe pyrene was compared with atomistic molecular dynamics simulations of the model drug fenofibrate (FENO). Subsequently, kinetic drug supersaturation and thermodynamic solubility experiments were conducted. As a result, the different polymers showed hydrophobic domain formation to a varying degree and the molecular simulations supported interpretation of fluorescence spectroscopy data. Molecular insights were gained into the conformational structure of how the polymers interacted with FENO in solution phase, which apart from nucleation and crystal growth effects, determined drug concentrations in solution. Notable was that even at the lowest polymer concentration of 0.01 %, w/v, there were polymer-specific solubilisation effects of FENO observed and the resulting reduction in apparent drug supersaturation provided relevant knowledge both from a mechanistic and practical perspective.
Keywords
Solubility, Pharmaceutical polymers, Hydrophobic domains, Drug supersaturation, Drug precipitation inhibition
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ISBN
ISSN
0928-0987
1879-0720
1879-0720
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
Gold
License
Citation
Zeneli, E., Lange, J. J., Holm, R., & Kuentz, M. (2024). A study of hydrophobic domain formation of polymeric drug precipitation inhibitors in aqueous solution. European Journal of Pharmaceutical Sciences, 198, 106791. https://doi.org/10.1016/j.ejps.2024.106791