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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Authors
O'Dwyer, Patrick J.
Box, Karl J.
Vertzoni, Maria
Reppas, Christos
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Publication date
2022
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01A - Journal article
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European Journal of Pharmaceutical Sciences
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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.
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600 - Technik, Medizin, angewandte Wissenschaften
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0928-0987
1879-0720
Language
English
Created during FHNW affiliation
Yes
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Published
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Peer review of the complete publication
Open access category
Gold
License
'https://creativecommons.org/licenses/by-nc-nd/4.0/'
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

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