A study of hydrophobic domain formation of polymeric drug precipitation inhibitors in aqueous solution
Autor:innen
Autor:in (Körperschaft)
Publikationsdatum
01.07.2024
Typ der Arbeit
Studiengang
Sammlung
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
European Journal of Pharmaceutical Sciences
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
198
Ausgabe / Nummer
Seiten / Dauer
106791
Patentnummer
Verlag / Herausgebende Institution
Elsevier
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
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.
Schlagwörter
Solubility, Pharmaceutical polymers, Hydrophobic domains, Drug supersaturation, Drug precipitation inhibition
Fachgebiet (DDC)
600 - Technik, Medizin, angewandte Wissenschaften
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
0928-0987
1879-0720
1879-0720
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Zukunftsfelder FHNW
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Gold
Lizenz
Zitation
ZENELI, Egis, Justus Johann LANGE, René HOLM und Martin KUENTZ, 2024. A study of hydrophobic domain formation of polymeric drug precipitation inhibitors in aqueous solution. European Journal of Pharmaceutical Sciences. 1 Juli 2024. Bd. 198, S. 106791. DOI 10.1016/j.ejps.2024.106791. Verfügbar unter: https://doi.org/10.26041/fhnw-11635