Bowel MRI imaging to investigate drug delivery from coated capsules

Sulaiman, Sarah (2023) Bowel MRI imaging to investigate drug delivery from coated capsules. PhD thesis, University of Nottingham.

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Magnetic resonance imaging (MRI) has the potential to provide new physiological insights into oral dosage forms in the undisturbed human GI tract. This potential has been recently shown in the literature, however these initial studies principally focused on the upper GI tract. Applications to the lower GI tract and particularly to MRI imaging of coated capsules remain to be explored to date.


Building on the available literature, this work therefore aimed to:

1. Design and manufacture coated capsules with the potential to reach the lower human intestine and at the same time to be MRI-visible

2. Develop and demonstrate a new MRI method to track the transit of the coated capsule and its disintegration in the lower human intestine

3. Load the coated capsule with an active pharmaceutical ingredient (API) and correlate the MRI findings with the API’s absorption kinetic

4. Explore additional MRI measurements of GI function of interest for oral dosage forms, such as small bowel motility measurements, by comparing MRI with concomitant perfused manometry

Key results

Size 0 (21 mm × 7 mm) capsules, consisting of a hydroxypropyl methylcellulose (HPMC) shell, dip-coated with different amounts of synthetic polymer Eudragit® S 100 were designed and manufactured manually in house. The capsules were filled with 0.65 mL of olive oil as MRI-visible marker fluid. Standard, basket apparatus disintegration tests showed that the capsules were able to withstand the upper gastrointestinal tract acid conditions and that disintegration time in intestinal condition increased with weight gain due to coating. The capsules could also be visualised in vitro using MRI. The in vivo imaging feasibility study in 10 healthy adult participants showed

that it was possible to track capsules with varying amounts of coating in the human gastrointestinal tract. The capsules’ loss of integrity was imaged exploiting the ability of MRI to image fat and water separately, and in

combination. By the 360 min end of the study, out of the 10 participants, the capsules were imaged in the small bowel in 9 participants, in the terminal ileum in 8 participants and in the colon in 4 participants. Loss of capsule’s

integrity was observed for 8 participants out of 10, occurring predominantly in distal intestinal regions.

After this, 75 mg of caffeine was added in suspension to the olive oil inside the capsules. The selection of this dose was based on literature searches and aimed to provide a safe active pharmaceutical ingredient marker, and also a marker that could be adequately absorbed from the unfavourable

environment of the large intestine and then be detected in saliva. For this purpose, a pre-existing high-performance liquid chromatography (HPLC) assay was used. The conditions, peak shapes and run time for the injections were optimised for this study and the assay’s lower limits of detection

characterised. Nine healthy participants were then administered capsules manufactured with varying amounts of Eudragit® S 100 coating from 0 mg to 36 mg weight gain. The timing of the first loss of capsule integrity detected in

the body using MRI correlated well with the onset of increase in caffeine concentration in the saliva from the baseline level (R2 = 0.76, p = 0.0022). Lastly, the work explored the ability of MRI to monitor small bowel motility

using retrospective data whereby 18 healthy volunteers underwent concomitant MRI and perfused manometry monitoring of duodenal motility. Total of 393 data sets could be compared showing limitations of the MRI protocol and a modest (R2 = 0.1214) but significant (p < 0.0001) correlation between the values of motility indexes derived from MRI and corresponding perfused manometry values. The association between MRI peaks of motility and MMC III events was statistically significant (p < 0.0001).


Building on initial reports in the literature this work has successfully developed and tested in vivo a coated capsule using a new concept for the MRI-visible filling. MRI was able to determine location and disintegration times of these coated capsules in the distal intestine, and this correlated well with absorption kinetics of a model active pharmaceutical ingredient, caffeine in this case. This work adds to the field new methods to study performance of coated

capsules in vivo in an undisturbed bowel. The new data and techniques will in turn help to make in vitro pharmacopoieial tests and kinetic and bench dynamic modelling more in vivo relevant. MRI has also the potential to assess other parameters of gastrointestinal function which are relevant for dosage form transit and disintegration such as small bowel motility. However such

methods have limitations and more work to incorporate them with the MRI tracking of coated capsules remains to be done.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Marciani, Luca
Stolnik, Snow
Gershkovich, Pavel
Spiller, Robin
Keywords: modified release; capsules; colon; large intestine; drug absorption; lower intestine; MRI; Magnetic Resonance Imaging
Subjects: QS-QZ Preclinical sciences (NLM Classification) > QV Pharmacology
W Medicine and related subjects (NLM Classification) > WI Digestive system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 74604
Depositing User: Sulaiman, Sarah
Date Deposited: 13 Dec 2023 04:40
Last Modified: 13 Dec 2023 04:40

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