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The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study

Controlling the time point and site of the release of active ingredients within the gastrointestinal tract after administration of oral delivery systems is still a challenge. In this study, the effect of the combination of small capsules (size 3) and large capsules (size 00) on the disintegration si...

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Autores principales: Rump, Adrian, Weiss, Franziska N., Schulz, Louisa, Kromrey, Marie-Luise, Scheuch, Eberhard, Tzvetkov, Mladen V., White, Tyler, Durkee, Shane, Judge, Kevin W., Jannin, Vincent, Bellamine, Aouatef, Weitschies, Werner, Grimm, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707024/
https://www.ncbi.nlm.nih.gov/pubmed/34959284
http://dx.doi.org/10.3390/pharmaceutics13122002
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author Rump, Adrian
Weiss, Franziska N.
Schulz, Louisa
Kromrey, Marie-Luise
Scheuch, Eberhard
Tzvetkov, Mladen V.
White, Tyler
Durkee, Shane
Judge, Kevin W.
Jannin, Vincent
Bellamine, Aouatef
Weitschies, Werner
Grimm, Michael
author_facet Rump, Adrian
Weiss, Franziska N.
Schulz, Louisa
Kromrey, Marie-Luise
Scheuch, Eberhard
Tzvetkov, Mladen V.
White, Tyler
Durkee, Shane
Judge, Kevin W.
Jannin, Vincent
Bellamine, Aouatef
Weitschies, Werner
Grimm, Michael
author_sort Rump, Adrian
collection PubMed
description Controlling the time point and site of the release of active ingredients within the gastrointestinal tract after administration of oral delivery systems is still a challenge. In this study, the effect of the combination of small capsules (size 3) and large capsules (size 00) on the disintegration site and time was investigated using magnetic resonance imaging (MRI) in combination with a salivary tracer technique. As capsule shells, Vcaps(®) HPMC capsules, Vcaps(®) Plus HPMC capsules, gelatin and DRcaps(®) designed release capsules were used. The three HPMC-based capsules (Vcaps(®), Vcaps(®) Plus and DRcaps(®) capsules) were tested as single capsules; furthermore, seven DUOCAP(®) capsule-in-capsule combinations were tested in a 10-way crossover open-label study in six healthy volunteers. The capsules contained iron oxide and hibiscus tea powder as tracers for visualization in MRI, and two different caffeine species (natural caffeine and (13)C(3)) to follow caffeine release and absorption as measured by salivary levels. Results showed that the timing and location of disintegration in the gastrointestinal tract can be measured and differed when using different combinations of capsule shells. Increased variability among the six subjects was observed in most of the capsule combinations. The lowest variability in gastrointestinal localization of disintegration was observed for the DUOCAP(®) capsule-in-capsule configuration using a DRcaps(®) designed release capsule within a DRcaps(®) designed release outer capsule. In this combination, the inner DRcaps(®) designed release capsule always opened reliably after reaching the ileum. Thus, this combination enables targeted delivery to the distal small intestine. Among the single capsules tested, Vcaps(®) Plus HPMC capsules showed the fastest and most consistent disintegration.
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spelling pubmed-87070242021-12-25 The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study Rump, Adrian Weiss, Franziska N. Schulz, Louisa Kromrey, Marie-Luise Scheuch, Eberhard Tzvetkov, Mladen V. White, Tyler Durkee, Shane Judge, Kevin W. Jannin, Vincent Bellamine, Aouatef Weitschies, Werner Grimm, Michael Pharmaceutics Article Controlling the time point and site of the release of active ingredients within the gastrointestinal tract after administration of oral delivery systems is still a challenge. In this study, the effect of the combination of small capsules (size 3) and large capsules (size 00) on the disintegration site and time was investigated using magnetic resonance imaging (MRI) in combination with a salivary tracer technique. As capsule shells, Vcaps(®) HPMC capsules, Vcaps(®) Plus HPMC capsules, gelatin and DRcaps(®) designed release capsules were used. The three HPMC-based capsules (Vcaps(®), Vcaps(®) Plus and DRcaps(®) capsules) were tested as single capsules; furthermore, seven DUOCAP(®) capsule-in-capsule combinations were tested in a 10-way crossover open-label study in six healthy volunteers. The capsules contained iron oxide and hibiscus tea powder as tracers for visualization in MRI, and two different caffeine species (natural caffeine and (13)C(3)) to follow caffeine release and absorption as measured by salivary levels. Results showed that the timing and location of disintegration in the gastrointestinal tract can be measured and differed when using different combinations of capsule shells. Increased variability among the six subjects was observed in most of the capsule combinations. The lowest variability in gastrointestinal localization of disintegration was observed for the DUOCAP(®) capsule-in-capsule configuration using a DRcaps(®) designed release capsule within a DRcaps(®) designed release outer capsule. In this combination, the inner DRcaps(®) designed release capsule always opened reliably after reaching the ileum. Thus, this combination enables targeted delivery to the distal small intestine. Among the single capsules tested, Vcaps(®) Plus HPMC capsules showed the fastest and most consistent disintegration. MDPI 2021-11-25 /pmc/articles/PMC8707024/ /pubmed/34959284 http://dx.doi.org/10.3390/pharmaceutics13122002 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
Rump, Adrian
Weiss, Franziska N.
Schulz, Louisa
Kromrey, Marie-Luise
Scheuch, Eberhard
Tzvetkov, Mladen V.
White, Tyler
Durkee, Shane
Judge, Kevin W.
Jannin, Vincent
Bellamine, Aouatef
Weitschies, Werner
Grimm, Michael
The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study
title The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study
title_full The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study
title_fullStr The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study
title_full_unstemmed The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study
title_short The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study
title_sort effect of capsule-in-capsule combinations on in vivo disintegration in human volunteers: a combined imaging and salivary tracer study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707024/
https://www.ncbi.nlm.nih.gov/pubmed/34959284
http://dx.doi.org/10.3390/pharmaceutics13122002
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