Assessing Gastric Emptying of Gastro-Resistant Capsules in Pigs: Impact of Capsule Size

This poster was presented at the AAPS 2025:

PURPOSE

Reliable pre-clinical large animal models are vital during drug development
Pigs are a promising model for oral drug delivery due to anatomical and physiological similarities to humans [1].
Large monolithic capsules show prolonged gastric retention, raising concerns about translatability [2].
This limitation can potentially be addressed by administering prokinetic agents [3].
This study investigates gastric emptying of gastro-resistant Capsugel® Enprotect ® capsules (sizes 0 2) and evaluates metoclopramide as a prokinetic intervention in the landrace pig model through pharmacokinetic analysis of rapidly absorbed marker compounds.

OBJECTIVE(S)

Assess gastric emptying of enteric capsules of varying sizes in pigs
Evaluate metoclopramide´s effect on capsule transit
Validate capsule endoscopy for in vivo imaging of gastric emptying
Generate insights into the pig as a preclinical model

METHOD(S)

Design: Non-randomized, four-way crossover in fasted Landrace pigs Treatments:

Sizes 0, 1, and 2 capsules (paracetamol payload)
Size 1 + metoclopramide (0.5 mg/kg i.m.)
Capsule endoscope in 5 pigs
Concurrent caffeine immediate-release (IR) tablets for dual PK markers

Sampling: 0-24 h plasma collection, LLE-HPLC quantification

Figure 1. Schematic representation of Capsugel® Enprotect® capsule sizes (0, 1, 2) tested in vivo, each filled with paracetamol (200 350 mg) as a pharmacokinetic marker. ALICAM® capsule endoscopes were roadministered in selected study legs to visually assess gastric transit.

Figure 2. Overview of the study design in landrace pigs: one leg included intramuscular metoclopramide(0.5 mg/kg) 30 min prior to oral dosing. All pigs received one of three capsule sizes (0, 1, or 2) containing paracetamol, alongside caffeine IR tablets (100 mg). Blood samples were collected over 24 h and analysed via liquid-liquid extraction followed by HPLC. — Figure 2. Overview of the study design in landrace pigs: one leg included intramuscular metoclopramide (0.5 mg/kg) 30 min prior to oral dosing. All pigs received one of three capsule sizes (0, 1, or 2) containing paracetamol, alongside caffeine IR tablets (100 mg). Blood samples were collected over 24 h and analysed via liquid-liquid extraction followed by HPLC.

RESULT(S)

Influence of Capsule Size

All capsule sizes emptied from the stomach (MAT: 3.9 8.1 h)
No significant differences between sizes, but trend toward slower emptying with larger capsules

Comparison to Immediate Release

No significant differences between IR tablets and gastro-protective capsules
Gastric residence longer than in humans for both IR tablets and gastro-protective capsules

Influence of Metoclopramide

No statistically significant acceleration of gastric emptying after MCP injection

Capsule Endoscopy

Gastric retention of capsule endoscopes for prolonged time
Visualisation of the gastric emptying process was unsuccessful due to problems with resolution and capsules moving out of the camera´s focus

CONCLUSION(S)

All gastro-resistant capsules showed mean absorption times of 3.9-8.1 hours, supporting their use in pig studies.
Gastric emptying in pigs was found to be longer than in humans, necessitating careful consideration in human scaling predictions
Metoclopramide did not significantly influence gastric emptying, suggesting that it does not offer substantial benefits.
Visualisation of the gastric emptying process was not feasible using a capsule endoscope.

These findings contribute to a more comprehensive understanding of the performance of non-disintegrating oral dosage forms in pigs and can guide on scaling factors in pig-human translation.

ACKNOWLEDGEMENTS

The study was conducted in compliance with the license granted by the Health Products Regulatory Authority (HPRA) of Ireland under the European Union (Protection of Animals Used for Scientific Purposes) Regulations 2012 (as amended) and Directive 2010/63/EU of the European Parliament (license number AE19130/P202). Ethical approval was obtained from the local university ethics committee.
Funding for this publication is provided under the GENEGUT (https://genegut.eu/) project funded by the European Commission as a Horizon Europe Research and Innovation Action (RIA) under the call tools and technologies for a healthy society (2021) (HORIZON-HLTH-2021-TOOL-06).

See the full poster on Assessing Gastric Emptying of Gastro-Resistant Capsules in Pigs: Impact of Capsule Size here

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Source: S. V. Hoffmann, B. T. Griffin, V. Jannin, J. P. O´Shea, poster Assessing Gastric Emptying of Gastro-Resistant Capsules in Pigs: Impact of Capsule Size, School of Pharmacy, University College Cork, Cork, Ireland, Capsugel France SAS, Colmar, France, GENE GUT. AAPS 2025