Exploring the cocrystal landscape of posaconazole by combining high-throughput screening experimentation with computational chemistry
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Dateien
Autor:innen
Autor:in (Körperschaft)
Publikationsdatum
23.12.2022
Typ der Arbeit
Studiengang
Sammlung
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Crystal Growth & Design
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
23
Ausgabe / Nummer
2
Seiten / Dauer
842-852
Patentnummer
Verlag / Herausgebende Institution
American Chemical Society
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
The development of multicomponent crystal forms, such as cocrystals, represents a means to enhance the dissolution and absorption properties of poorly water-soluble drug compounds. However, the successful discovery of new pharmaceutical cocrystals remains a time- and resource-consuming process. This study proposes the use of a combined computational-experimental high-throughput approach as a tool to accelerate and improve the efficiency of cocrystal screening exemplified by posaconazole. First, we employed the COSMOquick software to preselect and rank cocrystal candidates (coformers). Second, high-throughput crystallization experiments (HTCS) were conducted on the selected coformers. The HTCS results were successfully reproduced by liquid-assisted grinding and reaction crystallization, ultimately leading to the synthesis of thirteen new posaconazole cocrystals (7 anhydrous, 5 hydrates, and 1 solvate). The posaconazole cocrystals were characterized by PXRD, 1H NMR, Fourier transform-Raman, thermogravimetry–Fourier transform infrared spectroscopy, and differential scanning calorimetry. In addition, the prediction performance of COSMOquick was compared to that of two alternative knowledge-based methods: molecular complementarity (MC) and hydrogen bond propensity (HBP). Although HBP does not perform better than random guessing for this case study, both MC and COSMOquick show good discriminatory ability, suggesting their use as a potential virtual tool to improve cocrystal screening.
Schlagwörter
Screening assays, Molecules, Molecular interactions, Granular materials, Drug discovery
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
1528-7483
1528-7505
1528-7505
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Hybrid
Lizenz
Zitation
GUIDETTI, Matteo, Rolf HILFIKER, Martin KUENTZ, Annette BAUER-BRANDL und Fritz BLATTER, 2022. Exploring the cocrystal landscape of posaconazole by combining high-throughput screening experimentation with computational chemistry. Crystal Growth & Design. 23 Dezember 2022. Bd. 23, Nr. 2, S. 842–852. DOI 10.1021/acs.cgd.2c01072. Verfügbar unter: https://doi.org/10.26041/fhnw-4627