A simple and inexpensive enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine

Abstract

Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of drugs to treat specific small intestinal disorders such as small bowel bacterial overgrowth and targeting molecules to interrogate or to deliver vaccines to the remote regions of the small intestine has proven difficult. There is an unmet need for methodologies to release probes/drugs to remote regions of the gastrointestinal tract in furthering our understanding of gut health and pathogenesis. In order to address this concern, we need to know how the regional delivery of a surrogate labeled test compound is handled and in turn, if delivered locally as a liquid or powder, the dynamics of its subsequent handling and metabolism. In the studies we report on in this paper, we chose 13 C sodium acetate ( 13 C-acetate), which is a stable isotope probe that once absorbed in the small intestine can be readily measured non-invasively by collection and analysis of 13 CO 2 in the breath. This would provide information of gastric emptying rates and an indication of the site of release and absorptive capacity. In a series of in vitro and in vivo pig experiments, we assessed the enteric-protective properties of a commercially available polymer EUDRAGIT ® L100-55 on gelatin capsules and also on DRcaps ® . Test results demonstrated that DRcaps ® coated with EUDRAGIT ® L100-55 possessed enhanced enteric-protective properties, particularly in vivo. These studies add to the body of knowledge regarding gastric emptying in pigs and also begin the process of gathering specifications for the design of a simple and cost-effective enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.

Effects of Fecal Microbiome Transfer in Adolescents With Obesity

“… 4 Fecal microbiome was double encapsulated using delayed-release hydroxypropyl methylcellulose capsules (Capsugel), which were designed to remain intact during passage through the stomach, delivering their contents to the intestine. 18 , 19 , 20 Each participant received 7 capsules from each of the 4 same-sex donors. 4 Participants therefore received 28 capsules, which equated to approximately 22 g (wet weight) of fecal material (approximately 14 mL of frozen microbial suspension or saline) over 2 consecutive days.…”

“…Fecal microbiome was extracted from stools of 8 healthy donors (4 men, 4 women) who were selected following a rigorous screening protocol . Fecal microbiome was double encapsulated using delayed-release hydroxypropyl methylcellulose capsules (Capsugel), which were designed to remain intact during passage through the stomach, delivering their contents to the intestine . Each participant received 7 capsules from each of the 4 same-sex donors .…”

Achieving gastroresistance without coating: Formulation of capsule shells from enteric polymers

“…Previous attempts to produce enteric hard capsules have been reported in literature, however these rely on an additional coating step (AstraZeneca, 2017;Huyghebaert et al, 2004;Miller et al, 2015;Sharma and Sinha, 2018) or the incorporation of a gum which would provide protection to acid-sensitive ingredients by a delayed-release mechanism, such as DRCaps™ (Smith et al, 2010;Marzorati et al, 2015). These formulations do not exhibit a pH triggered release and instead rely on a time-delay in anticipation of timely emptying from stomach.…”

Developing Biologics Tablets: The Effects of Compression on the Structure and Stability of Bovine Serum Albumin and Lysozyme

“…The compression of biologics is a relatively new but critical unit operation with the potential to cause physical degradation of proteins/peptides because of exposure to mechanical, thermal, and shear stresses. , Finally, third is the enteric coating of tablets to protect the active pharmaceutical ingredient (API) from degradation in the upper GI tract. The polymeric enteric coating has been well established for lower molecular weight APIs but only successfully applied to biologics in a few cases (e.g., adenovirus vaccine tablets). − …”