In Vivo Evaluation of a Gastro-Resistant HPMC-Based “Next Generation Enteric” Capsule

Abstract

Many orally dosed APIs are bioavailable only when formulated as an enteric dosage form to protect them from the harsh environment of the stomach. However, an enteric formulation is often accompanied with a higher development effort in the first place and the potential degradation of fragile APIs during the coating process. Ready-to-use enteric hard capsules would be an easily available alternative to test and develop APIs in enteric formulations, while decreasing the time and cost of process development. In this regard, Lonza Capsugel® Next Generation Enteric capsules offer a promising approach as functional capsules. The in vivo performance of these capsules was observed with two independent techniques (MRI and caffeine in saliva) in eight human volunteers. No disintegration or content release in the stomach was observed, even after highly variable individual gastric residence times (range 7.5 to 82.5 min), indicating the reliable enteric properties of these capsules. Seven capsules disintegrated in the distal part of the small intestine; one capsule showed an uncommonly fast intestinal transit (15 min) and disintegrated in the colon. The results for this latter capsule by MRI and caffeine appearance differed dramatically, whereas for all other capsules disintegrating in the small intestine, the results were very comparable, which highlights the necessity for reliable and complementary measurement methods. No correlation could be found between the gastric residence time and disintegration after gastric emptying, which confirms the robust enteric formulation of those capsules.

Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review

“…This in combination with its robust nature made it straightforward to incorporate into both capsule shells and tablet dosage form types. This powerful feature was ideal for testing and developing gastroresistant capsules, ,, where disintegration of the capsule shell was delayed until it reached the intestine.…”

“…The use of magnetite was explored for the determination of the disintegration site and time for dosage forms, predominantly capsules. However, in several studies, ,,, problems determining exact disintegration site and time were reported due to the large size of the susceptibility feature of magnetite. This limitation was addressed by Grimm in a study where they made a clear distinction not to define a capsule rupture, but a process of “dispersion”, defined as the appearance of several small artifacts or a change in the size or the geometry of the artifact.…”

Enteric-Coated Capsules Providing Reliable Site-Specific Drug Delivery to the Distal Ileum

“…21,24,27,28,31,33 Reliable identification of drug delivery systems in MRI images requires either a unique signal or a combination of signals resulting in an identifiable signature. 15,16,19 In this study, we used ferrimagnetic black iron oxide (magnetite) as a tracer for the coated capsule because it produces a characteristic susceptibility artifact in the applied TRUFI sequence. In principle, other ferro-or ferrimagnetic substances, such as iron or nickel, could be used as well.…”

“…Once it is released from the capsule into the intestine, caffeine dissolves very quickly because of its high solubility and is rapidly absorbed, appearing in saliva almost immediately . Accordingly, the appearance of caffeine in saliva provides a sensitive measure of capsule disintegration. − …”

“…The observed gastric emptying times are very consistent with gastric emptying data for monolithic dosage forms that do not disintegrate in the stomach, such as enteric-coated tablets and capsules, when they are ingested in the fasted state. 19,21 The individual salivary caffeine concentrations of all subjects are shown in Figure 6A. Baseline salivary caffeine concentrations were below the LLOQ in all subjects except Subject 008 (Figure 3).…”