On the usefulness of four in vitro methods in assessing the intraluminal performance of poorly soluble, ionisable compounds in the fasted state
Authors
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Publication date
2022
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01A - Journal article
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Parent work
European Journal of Pharmaceutical Sciences
Special issue
DOI of the original publication
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Volume
168
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Elsevier
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Abstract
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.
Keywords
Subject (DDC)
600 - Technik, Medizin, angewandte Wissenschaften
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ISBN
ISSN
0928-0987
1879-0720
1879-0720
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
Gold
License
Citation
O’DWYER, Patrick J., Karl J. BOX, Georgios IMANIDIS, Maria VERTZONI und Christos REPPAS, 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. 2022. Bd. 168. DOI 10.1016/j.ejps.2021.106034. Verfügbar unter: https://doi.org/10.26041/fhnw-4362