{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:23:38Z","timestamp":1789565018728,"version":"build-2803163510"},"reference-count":19,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lonza Capsules &amp; Health Ingredients (Morristown, NJ, USA)","award":["n.a."],"award-info":[{"award-number":["n.a."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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\u00ae HPMC capsules, Vcaps\u00ae Plus HPMC capsules, gelatin and DRcaps\u00ae designed release capsules were used. The three HPMC-based capsules (Vcaps\u00ae, Vcaps\u00ae Plus and DRcaps\u00ae capsules) were tested as single capsules; furthermore, seven DUOCAP\u00ae 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 13C3) 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\u00ae capsule-in-capsule configuration using a DRcaps\u00ae designed release capsule within a DRcaps\u00ae designed release outer capsule. In this combination, the inner DRcaps\u00ae 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\u00ae Plus HPMC capsules showed the fastest and most consistent disintegration.<\/jats:p>","DOI":"10.3390\/pharmaceutics13122002","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:22:56Z","timestamp":1638314576000},"page":"2002","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Adrian","family":"Rump","sequence":"first","affiliation":[{"name":"Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska N.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa","family":"Schulz","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-7303","authenticated-orcid":false,"given":"Marie-Luise","family":"Kromrey","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology and Neuroradiology, University Hospital Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eberhard","family":"Scheuch","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, University Hospital Greifswald, 17487 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mladen V.","family":"Tzvetkov","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, University Hospital Greifswald, 17487 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"White","sequence":"additional","affiliation":[{"name":"Lonza Capsules & Health Ingredients, Morristown, NJ 07960, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0162-5865","authenticated-orcid":false,"given":"Shane","family":"Durkee","sequence":"additional","affiliation":[{"name":"Lonza Capsules & Health Ingredients, Morristown, NJ 07960, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin W.","family":"Judge","sequence":"additional","affiliation":[{"name":"Lonza Capsules & Health Ingredients, Morristown, NJ 07960, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1630-2807","authenticated-orcid":false,"given":"Vincent","family":"Jannin","sequence":"additional","affiliation":[{"name":"Lonza Capsules & Health Ingredients, 68000 Colmar, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1894-2939","authenticated-orcid":false,"given":"Aouatef","family":"Bellamine","sequence":"additional","affiliation":[{"name":"Lonza Capsules & Health Ingredients, Morristown, NJ 07960, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3492-7747","authenticated-orcid":false,"given":"Werner","family":"Weitschies","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1310-7435","authenticated-orcid":false,"given":"Michael","family":"Grimm","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ijpharm.2005.03.032","article-title":"In vitro evaluation of coating polymers for enteric coating and human ileal targeting","volume":"298","author":"Huyghebaert","year":"2005","journal-title":"Int. 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