Guiding excipient selection for physically stable amorphous solid dispersions: A combined in-vitro in-silico approach
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Autor:in (Körperschaft)
Publikationsdatum
06.2025
Typ der Arbeit
Studiengang
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
212
Ausgabe / Nummer
107152
Seiten / Dauer
Patentnummer
Verlag / Herausgebende Institution
Elsevier
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
Fast screening of amorphous solid dispersions (ASDs) is a need in the pharmaceutical industry. To support this, several emerging technologies have been developed ranging from in-silico prediction to miniaturized high-throughput experimentation. However, a notable challenge lies in the absence of comparative data. In the present work, a combination of a miniaturized screening of ASDs with calculation of activity coefficients using the conductor like screening model for real solvents (COSMO-RS) was proposed. First, the physical stability of ASDs comprising drugs of different glass forming ability (GFA) each with ten pharmaceutically relevant polymers was evaluated under accelerated stress conditions at two drug:polymer ratios. The miniaturized high-throughput screening method was based on the instability onset time that was monitored by polarized light microscopy (PLM). Furthermore, COSMO-RS was used to assess the interaction strength between the drugs and polymers by calculating activity coefficients, which was combined with estimations of the wet glass transition temperature (Tg), to account for molecular mobility. The computational calculations showed an overall alignment of 87 % with the instability of the ASDs observed experimentally for comparable drug:polymer ratios and humidity conditions. This positive result supports the current understanding of stable ASD formulation where at given ambient conditions, a low molecular mobility as well as the strength of interaction between drug and polymer has a main impact on the physical stability of ASDs. The current results are further encouraging to implement such a combined in-vitro/high-throughput (HTS) and in-silico strategy in early industrial screening of ASDs.
Schlagwörter
Amorphous solid dispersion, COSMO-RS, High-throughput screening, Physical stability
Fachgebiet (DDC)
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, E., Bohets, H., Mebenga, F. N., Holm, R., Tistaert, C., & Kuentz, M. (2025). Guiding excipient selection for physically stable amorphous solid dispersions: A combined in-vitro in-silico approach. European Journal of Pharmaceutical Sciences, 212(107152). https://doi.org/10.1016/j.ejps.2025.107152