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Towards a Better Understanding of the Post-Gastric Behavior of Enteric-Coated Formulations
PURPOSE: The aim of our work was to develop a biorelevant dissolution method for a better understanding of the in vivo performance of delayed-release tablet formulations. METHODS: The typical pH profile and residence times in the stomach and small intestine were determined in fasted conditions based...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837563/ https://www.ncbi.nlm.nih.gov/pubmed/35043354 http://dx.doi.org/10.1007/s11095-021-03163-0 |
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author | Katona, Miklós Tamás Kakuk, Melinda Szabó, Réka Tonka-Nagy, Péter Takács-Novák, Krisztina Borbás, Enikő |
author_facet | Katona, Miklós Tamás Kakuk, Melinda Szabó, Réka Tonka-Nagy, Péter Takács-Novák, Krisztina Borbás, Enikő |
author_sort | Katona, Miklós Tamás |
collection | PubMed |
description | PURPOSE: The aim of our work was to develop a biorelevant dissolution method for a better understanding of the in vivo performance of delayed-release tablet formulations. METHODS: The typical pH profile and residence times in the stomach and small intestine were determined in fasted conditions based on the published results of swallowable monitoring devices. Then, a multi-stage pH shift dissolution method was developed by adding different amounts of phosphate-based buffer solutions to the initial hydrochloric acid solution. Because of the highly variable in vivo residence times in the stomach, two alternatives of the method were applied, modeling rapid and slow gastric emptying as well. This approach provided an opportunity to study the effect of the acidic treatment on post gastric release. Six enteric-coated low-dose acetylsalicylic acid (ASA) formulations including the reference Aspirin Protect were tested as a model compound. Moreover, the thickness of the coating of each formulation was investigated by scanning electron microscope. RESULTS: Comparing the in vitro results to the known properties of the formulations, the new method was found to be more discriminative than the USP dissolution method. Ingredients affecting the in vitro dissolution, and thus probably the in vivo performance, were identified in both the tablet core and the coating of the tested formulations. The limited available in vivo data also indicated an increased predictivity. CONCLUSION: Overall, the presented method may be an efficient tool to support the development of enteric coated generic formulations. GRAPHICAL ABSTRACT: [Image: see text] |
format | Online Article Text |
id | pubmed-8837563 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-88375632022-02-23 Towards a Better Understanding of the Post-Gastric Behavior of Enteric-Coated Formulations Katona, Miklós Tamás Kakuk, Melinda Szabó, Réka Tonka-Nagy, Péter Takács-Novák, Krisztina Borbás, Enikő Pharm Res Research Paper PURPOSE: The aim of our work was to develop a biorelevant dissolution method for a better understanding of the in vivo performance of delayed-release tablet formulations. METHODS: The typical pH profile and residence times in the stomach and small intestine were determined in fasted conditions based on the published results of swallowable monitoring devices. Then, a multi-stage pH shift dissolution method was developed by adding different amounts of phosphate-based buffer solutions to the initial hydrochloric acid solution. Because of the highly variable in vivo residence times in the stomach, two alternatives of the method were applied, modeling rapid and slow gastric emptying as well. This approach provided an opportunity to study the effect of the acidic treatment on post gastric release. Six enteric-coated low-dose acetylsalicylic acid (ASA) formulations including the reference Aspirin Protect were tested as a model compound. Moreover, the thickness of the coating of each formulation was investigated by scanning electron microscope. RESULTS: Comparing the in vitro results to the known properties of the formulations, the new method was found to be more discriminative than the USP dissolution method. Ingredients affecting the in vitro dissolution, and thus probably the in vivo performance, were identified in both the tablet core and the coating of the tested formulations. The limited available in vivo data also indicated an increased predictivity. CONCLUSION: Overall, the presented method may be an efficient tool to support the development of enteric coated generic formulations. GRAPHICAL ABSTRACT: [Image: see text] Springer US 2022-01-18 2022 /pmc/articles/PMC8837563/ /pubmed/35043354 http://dx.doi.org/10.1007/s11095-021-03163-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Paper Katona, Miklós Tamás Kakuk, Melinda Szabó, Réka Tonka-Nagy, Péter Takács-Novák, Krisztina Borbás, Enikő Towards a Better Understanding of the Post-Gastric Behavior of Enteric-Coated Formulations |
title | Towards a Better Understanding of the Post-Gastric Behavior of Enteric-Coated Formulations |
title_full | Towards a Better Understanding of the Post-Gastric Behavior of Enteric-Coated Formulations |
title_fullStr | Towards a Better Understanding of the Post-Gastric Behavior of Enteric-Coated Formulations |
title_full_unstemmed | Towards a Better Understanding of the Post-Gastric Behavior of Enteric-Coated Formulations |
title_short | Towards a Better Understanding of the Post-Gastric Behavior of Enteric-Coated Formulations |
title_sort | towards a better understanding of the post-gastric behavior of enteric-coated formulations |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837563/ https://www.ncbi.nlm.nih.gov/pubmed/35043354 http://dx.doi.org/10.1007/s11095-021-03163-0 |
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