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Towards a Better Understanding of Verapamil Release from Kollicoat SR:IR Coated Pellets Using Non-Invasive Analytical Tools
The aim of this study was to gain deeper insight into the mass transport mechanisms controlling drug release from polymer-coated pellets using non-invasive analytical tools. Pellet starter cores loaded with verapamil HCl (10% loading, 45% lactose, 45% microcrystalline cellulose) were prepared by ext...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541620/ https://www.ncbi.nlm.nih.gov/pubmed/34684015 http://dx.doi.org/10.3390/pharmaceutics13101723 |
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author | Fahier, Julie Vukosavljevic, Branko De Kinder, Laure Florin, Hugues Goossens, Jean-François Windbergs, Maike Siepmann, Florence Siepmann, Juergen Muschert, Susanne |
author_facet | Fahier, Julie Vukosavljevic, Branko De Kinder, Laure Florin, Hugues Goossens, Jean-François Windbergs, Maike Siepmann, Florence Siepmann, Juergen Muschert, Susanne |
author_sort | Fahier, Julie |
collection | PubMed |
description | The aim of this study was to gain deeper insight into the mass transport mechanisms controlling drug release from polymer-coated pellets using non-invasive analytical tools. Pellet starter cores loaded with verapamil HCl (10% loading, 45% lactose, 45% microcrystalline cellulose) were prepared by extrusion/spheronization and coated with 5% Kollicoat SR:IR 95:5 or 10% Kollicoat SR:IR 90:10. Drug release was measured from ensembles of pellets as well as from single pellets upon exposure to acetate buffer pH = 3.5 and phosphate buffer pH = 7.4. The swelling of single pellets was observed by optical microscopy, while dynamic changes in the pH in the pellet cores were monitored by fluorescence spectroscopy. Also, mathematical modeling using a mechanistically realistic theory as well as SEM and Raman imaging were applied to elucidate whether drug release mainly occurs by diffusion through the intact film coatings or whether crack formation in the film coatings plays a role. Interestingly, fluorescence spectroscopy revealed that the pH within the pellet cores substantially differed upon exposure to acetate buffer pH = 3.5 and phosphate buffer pH = 7.4, resulting in significant differences in drug solubility (verapamil being a weak base) and faster drug release at lower pH: from ensembles of pellets and single pellets. The monitoring of drug release from and the swelling of single pellets indicated that crack formation in the film coatings likely plays a major role, irrespective of the Kollicoat SR:IR ratio/coating level. This was confirmed by mathematical modeling, SEM and Raman imaging. Importantly, the latter technique allowed also for non-invasive measurements, reducing the risk of artifact creation associated with sample cutting with a scalpel. |
format | Online Article Text |
id | pubmed-8541620 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85416202021-10-24 Towards a Better Understanding of Verapamil Release from Kollicoat SR:IR Coated Pellets Using Non-Invasive Analytical Tools Fahier, Julie Vukosavljevic, Branko De Kinder, Laure Florin, Hugues Goossens, Jean-François Windbergs, Maike Siepmann, Florence Siepmann, Juergen Muschert, Susanne Pharmaceutics Article The aim of this study was to gain deeper insight into the mass transport mechanisms controlling drug release from polymer-coated pellets using non-invasive analytical tools. Pellet starter cores loaded with verapamil HCl (10% loading, 45% lactose, 45% microcrystalline cellulose) were prepared by extrusion/spheronization and coated with 5% Kollicoat SR:IR 95:5 or 10% Kollicoat SR:IR 90:10. Drug release was measured from ensembles of pellets as well as from single pellets upon exposure to acetate buffer pH = 3.5 and phosphate buffer pH = 7.4. The swelling of single pellets was observed by optical microscopy, while dynamic changes in the pH in the pellet cores were monitored by fluorescence spectroscopy. Also, mathematical modeling using a mechanistically realistic theory as well as SEM and Raman imaging were applied to elucidate whether drug release mainly occurs by diffusion through the intact film coatings or whether crack formation in the film coatings plays a role. Interestingly, fluorescence spectroscopy revealed that the pH within the pellet cores substantially differed upon exposure to acetate buffer pH = 3.5 and phosphate buffer pH = 7.4, resulting in significant differences in drug solubility (verapamil being a weak base) and faster drug release at lower pH: from ensembles of pellets and single pellets. The monitoring of drug release from and the swelling of single pellets indicated that crack formation in the film coatings likely plays a major role, irrespective of the Kollicoat SR:IR ratio/coating level. This was confirmed by mathematical modeling, SEM and Raman imaging. Importantly, the latter technique allowed also for non-invasive measurements, reducing the risk of artifact creation associated with sample cutting with a scalpel. MDPI 2021-10-18 /pmc/articles/PMC8541620/ /pubmed/34684015 http://dx.doi.org/10.3390/pharmaceutics13101723 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 Fahier, Julie Vukosavljevic, Branko De Kinder, Laure Florin, Hugues Goossens, Jean-François Windbergs, Maike Siepmann, Florence Siepmann, Juergen Muschert, Susanne Towards a Better Understanding of Verapamil Release from Kollicoat SR:IR Coated Pellets Using Non-Invasive Analytical Tools |
title | Towards a Better Understanding of Verapamil Release from Kollicoat SR:IR Coated Pellets Using Non-Invasive Analytical Tools |
title_full | Towards a Better Understanding of Verapamil Release from Kollicoat SR:IR Coated Pellets Using Non-Invasive Analytical Tools |
title_fullStr | Towards a Better Understanding of Verapamil Release from Kollicoat SR:IR Coated Pellets Using Non-Invasive Analytical Tools |
title_full_unstemmed | Towards a Better Understanding of Verapamil Release from Kollicoat SR:IR Coated Pellets Using Non-Invasive Analytical Tools |
title_short | Towards a Better Understanding of Verapamil Release from Kollicoat SR:IR Coated Pellets Using Non-Invasive Analytical Tools |
title_sort | towards a better understanding of verapamil release from kollicoat sr:ir coated pellets using non-invasive analytical tools |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541620/ https://www.ncbi.nlm.nih.gov/pubmed/34684015 http://dx.doi.org/10.3390/pharmaceutics13101723 |
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