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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/12/2002 |
| _version_ | 1797501556557348864 |
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| author | Adrian Rump Franziska N. Weiss Louisa Schulz Marie-Luise Kromrey Eberhard Scheuch Mladen V. Tzvetkov Tyler White Shane Durkee Kevin W. Judge Vincent Jannin Aouatef Bellamine Werner Weitschies Michael Grimm |
| author_facet | Adrian Rump Franziska N. Weiss Louisa Schulz Marie-Luise Kromrey Eberhard Scheuch Mladen V. Tzvetkov Tyler White Shane Durkee Kevin W. Judge Vincent Jannin Aouatef Bellamine Werner Weitschies Michael Grimm |
| author_sort | Adrian Rump |
| collection | DOAJ |
| 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<sup>®</sup> HPMC capsules, Vcaps<sup>®</sup> Plus HPMC capsules, gelatin and DRcaps<sup>®</sup> designed release capsules were used. The three HPMC-based capsules (Vcaps<sup>®</sup>, Vcaps<sup>®</sup> Plus and DRcaps<sup>®</sup> capsules) were tested as single capsules; furthermore, seven DUOCAP<sup>®</sup> 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 <sup>13</sup>C<sub>3</sub>) 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<sup>®</sup> capsule-in-capsule configuration using a DRcaps<sup>®</sup> designed release capsule within a DRcaps<sup>®</sup> designed release outer capsule. In this combination, the inner DRcaps<sup>®</sup> 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<sup>®</sup> Plus HPMC capsules showed the fastest and most consistent disintegration. |
| first_indexed | 2024-03-10T03:20:08Z |
| format | Article |
| id | doaj.art-23bb7f9e40bd4f1ca17bc2316b3eb792 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:20:08Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-23bb7f9e40bd4f1ca17bc2316b3eb7922023-11-23T10:04:34ZengMDPI AGPharmaceutics1999-49232021-11-011312200210.3390/pharmaceutics13122002The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer StudyAdrian Rump0Franziska N. Weiss1Louisa Schulz2Marie-Luise Kromrey3Eberhard Scheuch4Mladen V. Tzvetkov5Tyler White6Shane Durkee7Kevin W. Judge8Vincent Jannin9Aouatef Bellamine10Werner Weitschies11Michael Grimm12Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17489 Greifswald, GermanyDepartment of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17489 Greifswald, GermanyDepartment of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17489 Greifswald, GermanyDepartment of Diagnostic Radiology and Neuroradiology, University Hospital Greifswald, 17475 Greifswald, GermanyDepartment of Clinical Pharmacology, University Hospital Greifswald, 17487 Greifswald, GermanyDepartment of Clinical Pharmacology, University Hospital Greifswald, 17487 Greifswald, GermanyLonza Capsules & Health Ingredients, Morristown, NJ 07960, USALonza Capsules & Health Ingredients, Morristown, NJ 07960, USALonza Capsules & Health Ingredients, Morristown, NJ 07960, USALonza Capsules & Health Ingredients, 68000 Colmar, FranceLonza Capsules & Health Ingredients, Morristown, NJ 07960, USADepartment of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17489 Greifswald, GermanyDepartment of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17489 Greifswald, GermanyControlling 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<sup>®</sup> HPMC capsules, Vcaps<sup>®</sup> Plus HPMC capsules, gelatin and DRcaps<sup>®</sup> designed release capsules were used. The three HPMC-based capsules (Vcaps<sup>®</sup>, Vcaps<sup>®</sup> Plus and DRcaps<sup>®</sup> capsules) were tested as single capsules; furthermore, seven DUOCAP<sup>®</sup> 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 <sup>13</sup>C<sub>3</sub>) 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<sup>®</sup> capsule-in-capsule configuration using a DRcaps<sup>®</sup> designed release capsule within a DRcaps<sup>®</sup> designed release outer capsule. In this combination, the inner DRcaps<sup>®</sup> 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<sup>®</sup> Plus HPMC capsules showed the fastest and most consistent disintegration.https://www.mdpi.com/1999-4923/13/12/2002MRIsalivary tracerDUOCAP<sup>®</sup>capsule-in-capsuleHPMCin vivo disintegration |
| spellingShingle | Adrian Rump Franziska N. Weiss Louisa Schulz Marie-Luise Kromrey Eberhard Scheuch Mladen V. Tzvetkov Tyler White Shane Durkee Kevin W. Judge Vincent Jannin Aouatef Bellamine Werner Weitschies Michael Grimm The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study Pharmaceutics MRI salivary tracer DUOCAP<sup>®</sup> capsule-in-capsule HPMC in vivo disintegration |
| 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 | MRI salivary tracer DUOCAP<sup>®</sup> capsule-in-capsule HPMC in vivo disintegration |
| url | https://www.mdpi.com/1999-4923/13/12/2002 |
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