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

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). 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.