Evaluating drug absorption from enteric capsules in pigs: Impact of capsule size on gastric emptying

Abstract

The development of novel drug delivery systems is contingent on the availability of reliable preclinical animal models and their translatability to humans. The pig model is of particular interest in predicting dosage form-related factors in humans based on similar anatomical and physiological features. However, it has been reported that large non-disintegrating capsules show prolonged retention in the porcine stomach, which questions the utility of the pig model for exploring enteric dosage forms. The present study examined the gastric emptying of gastro-resistant Capsugel® Enprotect® capsules (sizes 0, 1, and 2).

Highlights

Landrace pigs are useful for evaluating gastro-resistant oral dosage form robustness and the impact of size on gastric emptying.

Visualisation of a gastro-resistant product is challenging using capsule endoscopy, but the method can be used to confirm the fasting state.

Even after administration of metoclopramide, gastric emptying in landrace pigs is longer than in humans for both IR and gastro-resistant products and translation of data to humans should be done cautiously.

The prokinetic agent metoclopramide was evaluated for its potential to enhance gastric emptying. Paracetamol and caffeine were used as marker drugs. Pharmacokinetic parameters were employed to assess gastric emptying, with blood samples collected over a 24-hour period. The study demonstrated that Capsugel® Enprotect® capsules were cleared from the stomach, with mean absorption times ranging from 3.9 to 8.1 hours. There was no statistically significant difference between the tested capsule sizes. However, a trend toward slower gastric emptying with increasing capsule size was observed.

In general, gastric emptying appeared to be slower than what is typically seen in humans, which limits the direct translatability of the findings. The administration of metoclopramide did not accelerate gastric emptying or improve consistency between individuals. Although the capsules emptied from the stomach more quickly than large monolithic dosage forms, the longer gastric residence compared to humans remains a limitation and should be taken into account when interpreting and extrapolating the data.

Download the full article as PDF here Evaluating drug absorption from enteric capsules in pigs

or read it here

Materials

Gastro-resistant Capsugel® Enprotect® capsules were provided by Capsugel France SAS (Colmar, France). PROPLUS® (G. R. Lane Health Products Ltd., UK) 50 mg caffeine IR tablets were sourced from a local pharmacy. Emeprid® 5mg/mL metoclopramide (MCP) solution for injection was obtained from the designated veterinarian. Ensure® Plus (Abbott Laboratories Ltd., Ireland) was purchased in a local pharmacy. Sodium chloride 0.9 % w/v (B249419) and glucose 5 % w/v (B249422) solutions were from Fresenius Kabi Deutschland GmbH (Bad Homburg, Germany). ALICAM® capsule endoscope was sourced from Infiniti Medical (Huddersfield, UK). HPLC-grade acetic acid (glacial, 10,365,020) and water (10,449,380) were obtained from Fisher Scientific Ireland (Dublin, Ireland). Methanol (34,860) and ethyl acetate (34,858), also of HPLC grade, were purchased from Merck Life Science Ltd (Carrigtwohill, Ireland). The internal standard (PHR1531), paracetamol (A5000), metoclopramide (M0763), and caffeine (C0750) were sourced from Merck Life Science Ltd (Carrigtwohill, Ireland).

Sophia V. Hoffmann, Brendan T. Griffin, Vincent Jannin, Joseph P. O’Shea, Evaluating drug absorption from enteric capsules in pigs: Impact of capsule size on gastric emptying, European Journal of Pharmaceutical Sciences,
Volume 213, 2025, 107237, ISSN 0928-0987, https://doi.org/10.1016/j.ejps.2025.107237.