Discovery of cilnidipine cocrystals with enhanced dissolution by the use of computational tools and semiautomatic high-throughput screening
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Autor:in (Körperschaft)
Publikationsdatum
29.04.2025
Typ der Arbeit
Studiengang
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
25
Ausgabe / Nummer
10
Seiten / Dauer
3374-3385
Patentnummer
Verlag / Herausgebende Institution
American Chemical Society
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
Cocrystals are an attractive option for overcoming drug limitations, such as a low dissolution rate and absorption of poorly water-soluble compounds. Nevertheless, the discovery of new cocrystals remains a trial-and-error approach in which hundreds of coformers and several experimental methods are often tested. To streamline the cocrystal screening, computational methods can be used to select the coformers most likely to form a cocrystal, while high-throughput screening (HTS) approaches can rapidly screen them experimentally. In this manuscript, a new cocrystal of the extremely poorly soluble drug cilnidipine (solubility ≈30 ng/mL, 0.06 μM) was successfully discovered by applying HTS approaches. Only one cocrystal resulted from the screening with a total of 52 coformers, whereby the computational approach molecular complementarity successfully ranked this coformer (p-toluenesulfonamide) at the third position of the screening list. Dissolution studies conducted on the cocrystal in blank FaSSIF (fasted-state simulated intestinal fluid) and FaSSIF pH 6.5 revealed enhanced drug dissolution with a maximum achieved supersaturation equal to seven times the solubility of the crystalline drug. Dissolution rates of drug and coformer were compared for better mechanistic understanding of the cocrystal dissolution–supersaturation–precipitation behavior. The case of cilnidipine with a rare occurrence of cocrystals emphasized the importance of using joint computational and HTS approaches to enable successful cocrystal identification for pharmaceutical development.
Schlagwörter
Crystals, Dissolution, Drug discovery, Molecules, Screening assays
Fachgebiet (DDC)
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
Zukunftsfelder FHNW
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Hybrid
Lizenz
Zitation
Guidetti, M., Hilfiker, R., De Paul, S. M., Bauer-Brandl, A., Blatter, F., & Kuentz, M. (2025). Discovery of cilnidipine cocrystals with enhanced dissolution by the use of computational tools and semiautomatic high-throughput screening. Crystal Growth & Design, 25(10), 3374–3385. https://doi.org/10.1021/acs.cgd.5c00184