Modified Polymer Matrix in Pharmaceutical Hot Melt Extrusion by Molecular Interactions with a Carboxylic Coformer
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Autor:innen
Autor:in (Körperschaft)
Publikationsdatum
2019
Typ der Arbeit
Studiengang
Sammlung
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Molecular Pharmaceutics
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
16
Ausgabe / Nummer
1
Seiten / Dauer
141 - 150
Patentnummer
Verlag / Herausgebende Institution
American Chemical Society
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
Hot melt extrusion (HME) has become an essential technology to cope with an increasing number of poorly soluble drug candidates. However, there is only a limited choice of pharmaceutical polymers for obtaining suitable amorphous solid dispersions (ASD). Considerations of miscibility, stability, and biopharmaceutical performance narrow the selection of excipients, and further technical constraints arise from needed pharmaceutical processing. The present work introduces the concept of molecularly targeted interactions of a coformer with a polymer to design a new matrix for HME. Model systems of dimethylaminoethyl methacrylate copolymer, Eudragit E (EE), and bicarboxylic acids were studied, and pronounced molecular interactions were demonstrated
by 1H, 13C NMR, FTIR spectroscopy, as well as by different techniques of microscopic imaging. A difference was shown between new formulations exploiting specifically the targeted molecular interactions and a common drug−polymer formulation. More specifically, a modified matrix with Malic acid exhibited a technical extrusion advantage over polymer alone, and there was a benefit of improved physical stability revealed for the drug fenofibrate. This model compound displayed greatly enhanced dissolution kinetics from the ASD formulations. It can be concluded that harnessing molecularly designed polymer modifications by coformers has much potential in solid dispersion technology and in particular regarding HME processing.
Schlagwörter
poorly water-soluble drug, hot melt extrusion, polymeric modification
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
DITZINGER, Felix, Uta Maria SCHERER, Monica SCHÖNENBERGER, Rene HOLM und Martin KUENTZ, 2019. Modified Polymer Matrix in Pharmaceutical Hot Melt Extrusion by Molecular Interactions with a Carboxylic Coformer. Molecular Pharmaceutics. 2019. Bd. 16, Nr. 1, S. 141 – 150. DOI 10.1021/acs.molpharmaceut.8b00920. Verfügbar unter: https://doi.org/10.26041/fhnw-3605