A Systematic Study of Molecular Interactions of Anionic Drugs with a Dimethylaminoethyl Methacrylate Copolymer Regarding Solubility Enhancement
Vorschaubild nicht verfügbar
Autor:innen
Autor:in (Körperschaft)
Publikationsdatum
2017
Typ der Arbeit
Studiengang
Sammlung
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Ãœbergeordnetes Werk
Molecular Pharmaceutics
Themenheft
Link
Reihe / Serie
Jahrgang / Band
14
Ausgabe / Nummer
4
Seiten / Dauer
1243–1250
Patentnummer
Verlag / Herausgebende Institution
American Chemical Society
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
The methacrylate-copolymer Eudragit EPO (EPO) has raised interest in solubility enhancement of anionic drugs. Effects on aqueous drug solubility at rather low polymer concentrations are barely known despite their importance upon dissolution and dilution of oral dosage forms. We provide evidence for substantial enhancement (factor 4–230) of aqueous solubility of poorly water-soluble anionic drugs induced by low (0.1–5% (w/w)) concentration of EPO for a panel of seven acidic crystalline drugs. Diffusion data (determined by 1H nuclear magnetic resonance spectroscopy) indicate that the solubility increasing effect monitored by quantitative ultraperformance liquid chromatography was caused primarily by molecular API polymer interactions in the bulk liquid phase. Residual solid API remained unaltered as tested by X-ray powder diffraction. The solubility enhancement (SE) revealed a significant rank correlation (rSpearman = −0.83) with rDiffAPI, where SE and rDiffAPI are defined ratios of solubility and diffusion coefficient in the presence and absence of EPO. SE decreased in the order of indomethacin, mefenamic acid, warfarin, piroxicam, furosemide, bezafibrate, and tolbutamide. The solubilizing effect was attributed to both ionic and hydrophobic interactions between drugs and EPO. The excellent solubilizing properties of EPO are highly promising for pharmaceutical development, and the data set provides first steps toward an understanding of drug–excipient interaction mechanisms.
Schlagwörter
acidic drugs, nuclear magnetic resonance (NMR) spectroscopy, polymer−drug interaction, solubility enhancement
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
1543-8384
1543-8392
1543-8392
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
KIRCHMEYER, Wiebke, Alfred ROSS, Nicole WYTTENBACH, Jochem ALSENZ und Martin KUENTZ, 2017. A Systematic Study of Molecular Interactions of Anionic Drugs with a Dimethylaminoethyl Methacrylate Copolymer Regarding Solubility Enhancement. Molecular Pharmaceutics. 2017. Bd. 14, Nr. 4, S. 1243–1250. DOI 10.1021/acs.molpharmaceut.6b01116. Verfügbar unter: http://hdl.handle.net/11654/25788