Computational support to explore ternary solid dispersions of challenging drugs using coformer and hydroxypropyl cellulose
Autor:in (Körperschaft)
Publikationsdatum
10.10.2024
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
21
Ausgabe / Nummer
11
Seiten / Dauer
5619–5631
Patentnummer
Verlag / Herausgebende Institution
American Chemical Society
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
A majority of drugs marketed in amorphous formulations have a good glass-forming ability, while compounds less stable in the amorphous state still pose a formulation challenge. This work explores ternary solid dispersions of two model drugs with a polymer (i.e., hydroxypropyl cellulose) and a coformer as stabilizing excipients. The aim was to introduce a computational approach by preselecting additives using solubility parameter intervals (i.e., overlap range of solubility parameter, ORSP) followed by more advanced COSMO-RS theory modeling. Thus, a mapping of calculated mixing enthalpy and melting points is proposed for in silico evaluation prior to hot melt extrusion. Following experimental testing of process feasibility, the selected formulations were tested for their physical stability using conventional bulk analytics and by confocal laser scanning and atomic force microscopy imaging. In line with the in silico screening, dl-malic and l-tartaric acid (20%, w/w) in HPC formulations showed no signs of early drug crystallization after 3 months. However, l-tartaric acid formulations displayed few crystals on the surface, which was likely a humidity-induced surface phenomenon. Although more research is needed, the conclusion is that the proposed computational small-scale extrusion approach of ternary solid dispersion has great potential in the formulation development of challenging drugs.
Schlagwörter
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
1543-8384
1543-8392
1543-8392
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Zukunftsfelder FHNW
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Hybrid
Lizenz
Zitation
NIEDERQUELL, Andreas, Susanne HERZIG, Monica SCHÖNENBERGER, Edmont STOYANOV und Martin KUENTZ, 2024. Computational support to explore ternary solid dispersions of challenging drugs using coformer and hydroxypropyl cellulose. Molecular Pharmaceutics. 10 Oktober 2024. Bd. 21, Nr. 11, S. 5619–5631. DOI 10.1021/acs.molpharmaceut.4c00592. Verfügbar unter: https://doi.org/10.26041/fhnw-11912