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. 2023 Nov 3;15(11):2576.
doi: 10.3390/pharmaceutics15112576.

In Vivo Evaluation of a Gastro-Resistant Enprotect® Capsule under Postprandial Conditions

Michael Grimm  1 , Adrian Rump  1 , Marie-Luise Kromrey  2 , Felix Morof  3 , Camille Dumont  4 , Vincent Jannin  4 , Mladen Vassilev Tzvetkov  3 , Werner Weitschies  1
Affiliations

In Vivo Evaluation of a Gastro-Resistant Enprotect® Capsule under Postprandial Conditions

Michael Grimm et al. Pharmaceutics. .

Abstract

Ready-to-fill enteric hard capsule shells are an evolving field of oral drug and nutraceutical products. Lonza Capsugel® Enprotect® capsules were recently proven to provide reliable release in the small intestine after fasted intake, but robustness against postprandial intake needed to be proven. In this study, the capsules were administered to 16 healthy young subjects after intake of a light meal. The Enprotect® capsules were labelled with 5 mg black iron oxide and 25 mg 13C3-caffeine. Magnetic Resonance Imaging was used to identify the localization and visual dispersion of the capsule filling. The salivary appearance of caffeine was considered a second independent and sensitive marker for the initial release. Whereas the fasted gastric residence time of the capsules amounted to 43 ± 32 min, it was increased to 158 ± 36 min after postprandial intake. Therefore, the mean dispersion time according to MRI and the mean caffeine appearance time were increased to 196 ± 37 min and 189 ± 37 min, respectively. But, similar to fasted administration, no capsule disintegration or leakage was observed in the stomach and 38% of the capsules disintegrated in the jejunum and 62% in the ileum. The mean dispersion time after gastric emptying and the mean caffeine appearance time after gastric emptying amounted to 38 ± 21 min and 31 ± 17 min, respectively. Both did not relevantly change compared to the fasted intake. Only the absolute dispersion time and caffeine appearance were prolonged due to the increased gastric residence and no relevant influence of the light meal was observed on the disintegration or release behavior of Enprotect® capsules after gastric emptying. The capsules also showed robust enteric properties after postprandial administration.

Keywords: MRI; caffeine; enteric hard capsule; fed state; hydroxypropyl methyl cellulose; hydroxypropyl methyl cellulose acetate succinate; saliva; stable isotope.

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Conflict of interest statement

The authors A.R., F.M., M.-L.K., M.V.T., W.W. and M.G. are only affiliated with the University of Greifswald and declare no conflict of interest. V.J. and C.D. are employees of the funder, which is the producer of the tested capsule shells. The funder influenced the study design and gave final permission for publication. Conduction of the study and interpretation of results were performed independently by the University of Greifswald. Conduction and interpretation of the study were not influenced by the funder.

Figures

Figure 1
Figure 1
Exemplary coronal images of one volunteer with an intact capsule represented by an intact susceptibility artifact of iron oxide at 60 min after capsule ingestion in the filled stomach, after 150 min in the proximal small intestine and dispersed artifacts after disintegration of the capsule at 165 min (arrows show the respective artifact, stomach with blue demarcation).
Figure 2
Figure 2
(A): Individual salivary caffeine concentrations with male subjects in black and females in grey (n = 16); (B): amplified exemplary caffeine profile with marking of calculated appearance time.
Figure 3
Figure 3
(A) Dispersion time (DT) as determined by MRI and 13C3-labelled caffeine appearance time (AT) in saliva, with gastric residence times (GRT) and DT and AT relative to gastric emptying, mean times marked by a horizontal bar (n = 16 each). (B) The site of dispersion as obtained from MRI tracking.
Figure 4
Figure 4
Dispersion time after gastric emptying (DT after GE) as determined by MRI after intake of Enprotect® capsules in fasted (n = 8) and fed state (n = 16). The mean disintegration time is marked by a horizontal bar. Fasted data from previous publication [2].
Figure 5
Figure 5
(A) Dispersion time after gastric emptying (DT after GE) and (B) caffeine appearance time after gastric emptying (AT after GE). Correlation is marked by a line; correlation coefficients and corresponding p-values are stated. (n = 16).
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