Interactions of dimethylaminoethyl methacrylate copolymer with non-acidic drugs demonstrated high solubilization in vitro and pronounced sustained release
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Autor:innen
Autor:in (Körperschaft)
Publikationsdatum
04/2018
Typ der Arbeit
Studiengang
Sammlung
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
European Journal of Pharmaceutics and Biopharmaceutics
Themenheft
DOI der Originalpublikation
Reihe / Serie
Reihennummer
Jahrgang / Band
125
Ausgabe / Nummer
Seiten / Dauer
68-75
Patentnummer
Verlag / Herausgebende Institution
Elsevier
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
Recent work demonstrated remarkable solubilization effects of methacrylate-copolymer Eudragit EPO (EPO) not only with acidic drugs but interestingly also with poorly soluble basic compounds. The current work studied EPO-mediated solubilization effects first in vitro using felodipine (FLP) and tamoxifen (TMX) as model compounds. EPO-containing solutions were subsequently compared in a rat pharmacokinetic study against reference solutions and suspensions. Surprisingly, solution formulations with EPO did not result in an increased relative oral bioavailability. Exposure was reduced for both drugs and plasma-profiles of the EPO solutions showed a delayed and lower maximum plasma concentration compared to the reference formulations. This sustained in vivo release was likely due to combined effects of strong drug-polymer interactions and pH-dependent precipitation of the polymer in the rat intestine. Remarkable was that in vitro drug-polymer coprecipitates did not reveal crystalline drug by polarized light microscopy. Thus, such a formulation approach provides a rather simple opportunity to modify drug release in vivo. However, this may be rather an approach for preclinical formulations, if high peak-to-trough ratios of plasma levels are problematic regarding adverse effects related to Cmax or if plasma concentrations drop too fast below required pharmacological concentrations
Schlagwörter
solubility enhancement, polymer drug interaction, Oral bioavailability, sustained release
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
0939-6411
1873-3441
1873-3441
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
SAAL, Wiebke, Nicole WYTTENBACH, Jochem ALSENZ und Martin KUENTZ, 2018. Interactions of dimethylaminoethyl methacrylate copolymer with non-acidic drugs demonstrated high solubilization in vitro and pronounced sustained release. European Journal of Pharmaceutics and Biopharmaceutics. April 2018. Bd. 125, S. 68–75. DOI 10.1016/j.ejpb.2018.01.006. Verfügbar unter: http://hdl.handle.net/11654/26983