Antifungal Activity of Econazole Nitrate/Cyclodextrin Complex: Effect of pH 2 and Formation of Complex Aggregates

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dc.contributorHáskóli Íslandsen_US
dc.contributorUniversity of Icelanden_US
dc.contributor.authorJansook, Phatsawee
dc.contributor.authorPrajapati, Manisha
dc.contributor.authorPruksakorn, Patamaporn
dc.contributor.authorLoftsson, Thorsteinn
dc.contributor.departmentLyfjafræðideild (HÍ)en_US
dc.contributor.departmentFaculty of Pharmaceutical Sciences (UI)en_US
dc.contributor.schoolSchool of Health Sciences (UI)en_US
dc.contributor.schoolHeilbrigðisvísindasvið (HÍ)en_US
dc.date.accessioned2021-02-24T13:16:26Z
dc.date.available2021-02-24T13:16:26Z
dc.date.issued2019-11
dc.description.abstractEconazole nitrate (ECN) is a weakly basic drug with very low aqueous solubility that hampers its permeation through biological membranes and results in low ECN bioavailability. Formation of drug/cyclodextrin (drug/CD) inclusion complexes is a formulation technology that can be applied to enhance drug solubility in aqueous media. The aim of this study was to determine the effect of CD complexation and pH adjustments on the ECN solubility. The ECN pHsolubility and ECN/CD phase-solubility profiles were determined. The solubility of ECN in aqueous acidic solutions containing α-cyclodextrin (αCD) was relatively high and much higher than in aqueous γ-cyclodextrin (γCD) solutions under same conditions. The complexation efficiency of the ECN/CD complex was relatively low for the unionized drug. Formation of ECN/CD inclusion complex was verified by proton nuclear magnetic resonance spectroscopy. Formation of ECN/CD complexes enhanced the drug stability during autoclaving. γCD complexes self-assembled to form nanoand microparticles whereas αCD complexes had negligible tendency to selfassemble. Formation of CD complex nano- and microparticles was investigated by dynamic light scattering and by drug permeation through semipermeable membranes of different molecular weight cut-off. The largest aggregate fraction was observed for the unionized ECN in aqueous pH 7.5 solution containing high CD concentration, that is 10% (w/v) CD. It was shown that in acidic solutions ECN/αCD can enhance the antifungal activity to filamentous fungi. This was associated with the increased ECN solubility and increase of readily available ECN molecules in aqueous αCD solutions.en_US
dc.description.sponsorshipThis work was financially supported by European Union grant No. MSCA-ITN-2017-765441 (transMed), Thailand Research Fund grant No. RSA5980050 and Faculty of Pharmaceutical Sciences, University of Iceland.en_US
dc.description.versionPeer-reviewed (accepted version)en_US
dc.format.extent118896en_US
dc.identifier.citationJansook, P., Prajapati, M., Pruksakorn, P., & Loftsson, T. (2020). Antifungal activity of econazole nitrate/cyclodextrin complex: Effect of pH and formation of complex aggregates. International Journal of Pharmaceutics, 574, 118896. doi:https://doi.org/10.1016/j.ijpharm.2019.118896en_US
dc.identifier.doi10.1016/j.ijpharm.2019.118896is
dc.identifier.issn0378-5173
dc.identifier.journalInternational Journal of Pharmaceuticsen_US
dc.identifier.urihttps://hdl.handle.net/20.500.11815/2469
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/765441en_US
dc.relation.ispartofseriesInternational Journal of Pharmaceutics;574
dc.relation.urlhttps://doi.org/10.1016/j.ijpharm.2019.118896en_US
dc.rightsinfo:eu-repo/semantics/embargoedAccessen_US
dc.titleAntifungal Activity of Econazole Nitrate/Cyclodextrin Complex: Effect of pH 2 and Formation of Complex Aggregatesen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dcterms.licenseCreative Commons Attribution 4.0 Licenceen_US

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