On the usefulness of four in vitro methods in assessing the intraluminal performance of poorly soluble, ionisable compounds in the fasted state
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Autor:innen
Autor:in (Körperschaft)
Publikationsdatum
2022
Typ der Arbeit
Studiengang
Sammlung
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
168
Ausgabe / Nummer
Seiten / Dauer
Patentnummer
Verlag / Herausgebende Institution
Elsevier
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
A small-scale two-stage biphasic system, a small-scale two-stage dissolution-permeation system, the Erweka
mini-paddle apparatus, and the BioGIT system were evaluated for their usefulness in assessing the intraluminal
performance of two low solubility drugs in the fasted state, one with weakly acidic properties (tested in a salt
form, diclofenac potassium) and one with weakly alkaline properties [ritonavir, tested as an amorphous solid
dispersion (ASD) formulation].
In all in vitro methods, an immediate-release tablet and a powder formulation of diclofenac potassium were
both rapidly dissolved in Level II biorelevant media simulating the conditions in the upper small intestine.
Physiologically based biopharmaceutics (PBB) modelling for the tablet formulation resulted in a successful
simulation of the average plasma profile in adults, whereas for the powder formulation modelling indicated that
gastric emptying and transport through the intestinal epithelium limit the absorption rates.
Detailed information on the behaviour of the ritonavir ASD formulation under both simulated gastric and
upper small intestinal conditions were crucial for understanding the luminal performance. PBB modelling
showed that the dissolution and precipitation parameters, estimated from the Erweka mini-paddle apparatus
data and the small-scale two-stage biphasic system data, respectively, were necessary to adequately simulate the
average plasma profile after administration of the ritonavir ASD formulation. Simulation of the gastrointestinal
transfer process from the stomach to the small intestine was necessary to evaluate the effects of hypochlorhydric
conditions on the luminal performance of the ritonavir ASD formulation.
Schlagwörter
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
O’Dwyer, P. J., Box, K. J., Imanidis, G., Vertzoni, M., & Reppas, C. (2022). On the usefulness of four in vitro methods in assessing the intraluminal performance of poorly soluble, ionisable compounds in the fasted state. European Journal of Pharmaceutical Sciences, 168. https://doi.org/10.1016/j.ejps.2021.106034