Biorelevant drug solubility enhancement modeled by a linear solvation energy relationship
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Autor:innen
Autor:in (Körperschaft)
Publikationsdatum
2017
Typ der Arbeit
Studiengang
Sammlung
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Journal of Pharmaceutical Sciences
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
107
Ausgabe / Nummer
1
Seiten / Dauer
503-506
Patentnummer
Verlag / Herausgebende Institution
Elsevier
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
It is for the pharmaceutical sciences of vital importance to understand how drugs are solubilized in biorelevant media. However, the complexity of fasted state simulated intestinal fluid (FaSSIF) has so far hampered adequate solubility modeling. The present study focuses on apparently neutral compounds at physiological pH and a linear free energy relationship is introduced for biorelevant drug solubilization. Based on literature data of 40 compounds, the Abraham solvation descriptors were calculated from chemical structure to then predict the ratio of solubility enhancement log(SE) in FaSSIF compared to aqueous buffer solubility at pH 6.5. A suitable model was obtained with R2 of 0.810 and notable were especially the positive effect of McGowan's characteristic volume and the negative effect of drug basicity. A negative influence on log(SE) was further evidenced for dipolarity/polarizability and for the excess molar refraction descriptor. A positive solubilization effect was obtained for drug acidity and hence the tendency for proton donation, which was likely due to the different proton-accepting moieties of taurocholic acid and lecithin that are both present in the mixed colloids of FaSSIF. Overall, an improved understanding was achieved regarding the molecular features that are driving drug solubilization in biorelevant media.
Schlagwörter
solubility, in silico modeling, micelle, oral absorption, phospholipids
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
0022-3549
1520-6017
1520-6017
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Zukunftsfelder FHNW
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
Niederquell, A., & Kuentz, M. (2017). Biorelevant drug solubility enhancement modeled by a linear solvation energy relationship. Journal of Pharmaceutical Sciences, 107(1), 503–506. https://doi.org/10.1016/j.xphs.2017.08.017