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An In Vivo Predictive Dissolution Methodology (iPD Methodology) with a BCS Class IIb Drug Can Predict the In Vivo Bioequivalence Results: Etoricoxib Products

The purpose of this study was to predict in vivo performance of three oral products of Etoricoxib (Arcoxia(®) as reference and two generic formulations in development) by conducting in vivo predictive dissolution with GIS (Gastro Intestinal Simulator) and computational analysis. Those predictions we...

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Autores principales: Gonzalez-Alvarez, Isabel, Bermejo, Marival, Tsume, Yasuhiro, Ruiz-Picazo, Alejandro, Gonzalez-Alvarez, Marta, Hens, Bart, Garcia-Arieta, Alfredo, Amidon, Greg E., Amidon, Gordon L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067797/
https://www.ncbi.nlm.nih.gov/pubmed/33917118
http://dx.doi.org/10.3390/pharmaceutics13040507
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author Gonzalez-Alvarez, Isabel
Bermejo, Marival
Tsume, Yasuhiro
Ruiz-Picazo, Alejandro
Gonzalez-Alvarez, Marta
Hens, Bart
Garcia-Arieta, Alfredo
Amidon, Greg E.
Amidon, Gordon L.
author_facet Gonzalez-Alvarez, Isabel
Bermejo, Marival
Tsume, Yasuhiro
Ruiz-Picazo, Alejandro
Gonzalez-Alvarez, Marta
Hens, Bart
Garcia-Arieta, Alfredo
Amidon, Greg E.
Amidon, Gordon L.
author_sort Gonzalez-Alvarez, Isabel
collection PubMed
description The purpose of this study was to predict in vivo performance of three oral products of Etoricoxib (Arcoxia(®) as reference and two generic formulations in development) by conducting in vivo predictive dissolution with GIS (Gastro Intestinal Simulator) and computational analysis. Those predictions were compared with the results from previous bioequivalence (BE) human studies. Product dissolution studies were performed using a computer-controlled multicompartmental dissolution device (GIS) equipped with three dissolution chambers, representing stomach, duodenum, and jejunum, with integrated transit times and secretion rates. The measured dissolved amounts were modelled in each compartment with a set of differential equations representing transit, dissolution, and precipitation processes. The observed drug concentration by in vitro dissolution studies were directly convoluted with permeability and disposition parameters from literature to generate the predicted plasma concentrations. The GIS was able to detect the dissolution differences among reference and generic formulations in the gastric chamber where the drug solubility is high (pH 2) while the USP 2 standard dissolution test at pH 2 did not show any difference. Therefore, the current study confirms the importance of multicompartmental dissolution testing for weak bases as observed for other case examples but also the impact of excipients on duodenal and jejunal in vivo behavior.
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spelling pubmed-80677972021-04-25 An In Vivo Predictive Dissolution Methodology (iPD Methodology) with a BCS Class IIb Drug Can Predict the In Vivo Bioequivalence Results: Etoricoxib Products Gonzalez-Alvarez, Isabel Bermejo, Marival Tsume, Yasuhiro Ruiz-Picazo, Alejandro Gonzalez-Alvarez, Marta Hens, Bart Garcia-Arieta, Alfredo Amidon, Greg E. Amidon, Gordon L. Pharmaceutics Article The purpose of this study was to predict in vivo performance of three oral products of Etoricoxib (Arcoxia(®) as reference and two generic formulations in development) by conducting in vivo predictive dissolution with GIS (Gastro Intestinal Simulator) and computational analysis. Those predictions were compared with the results from previous bioequivalence (BE) human studies. Product dissolution studies were performed using a computer-controlled multicompartmental dissolution device (GIS) equipped with three dissolution chambers, representing stomach, duodenum, and jejunum, with integrated transit times and secretion rates. The measured dissolved amounts were modelled in each compartment with a set of differential equations representing transit, dissolution, and precipitation processes. The observed drug concentration by in vitro dissolution studies were directly convoluted with permeability and disposition parameters from literature to generate the predicted plasma concentrations. The GIS was able to detect the dissolution differences among reference and generic formulations in the gastric chamber where the drug solubility is high (pH 2) while the USP 2 standard dissolution test at pH 2 did not show any difference. Therefore, the current study confirms the importance of multicompartmental dissolution testing for weak bases as observed for other case examples but also the impact of excipients on duodenal and jejunal in vivo behavior. MDPI 2021-04-07 /pmc/articles/PMC8067797/ /pubmed/33917118 http://dx.doi.org/10.3390/pharmaceutics13040507 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gonzalez-Alvarez, Isabel
Bermejo, Marival
Tsume, Yasuhiro
Ruiz-Picazo, Alejandro
Gonzalez-Alvarez, Marta
Hens, Bart
Garcia-Arieta, Alfredo
Amidon, Greg E.
Amidon, Gordon L.
An In Vivo Predictive Dissolution Methodology (iPD Methodology) with a BCS Class IIb Drug Can Predict the In Vivo Bioequivalence Results: Etoricoxib Products
title An In Vivo Predictive Dissolution Methodology (iPD Methodology) with a BCS Class IIb Drug Can Predict the In Vivo Bioequivalence Results: Etoricoxib Products
title_full An In Vivo Predictive Dissolution Methodology (iPD Methodology) with a BCS Class IIb Drug Can Predict the In Vivo Bioequivalence Results: Etoricoxib Products
title_fullStr An In Vivo Predictive Dissolution Methodology (iPD Methodology) with a BCS Class IIb Drug Can Predict the In Vivo Bioequivalence Results: Etoricoxib Products
title_full_unstemmed An In Vivo Predictive Dissolution Methodology (iPD Methodology) with a BCS Class IIb Drug Can Predict the In Vivo Bioequivalence Results: Etoricoxib Products
title_short An In Vivo Predictive Dissolution Methodology (iPD Methodology) with a BCS Class IIb Drug Can Predict the In Vivo Bioequivalence Results: Etoricoxib Products
title_sort in vivo predictive dissolution methodology (ipd methodology) with a bcs class iib drug can predict the in vivo bioequivalence results: etoricoxib products
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067797/
https://www.ncbi.nlm.nih.gov/pubmed/33917118
http://dx.doi.org/10.3390/pharmaceutics13040507
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