Evaluation of Targeted-Release Capsule Formulations for Protection of the Acid-Sensitive Enzyme Pancreatin Under...

Objective: This study assessed the ability of capsule formulations to improve the oral delivery and retain activity of an acid-sensitive enzyme during gastrointestinal transit. Methods: The dissolution characteristics of five capsule formulations-single DRcaps^® [DR], single Vcaps^® Plus [VCP], and three DUOCAP^® capsule-in-capsule combinations, DRcaps^® inside DRcaps^® (DR-in-DR), DRcaps^® inside Vcaps^® Plus (DR-in-VCP), and Vcaps^® Plus inside DRcaps^® (VCP-in-DR)-were evaluated in an in vitro simulation of a healthy human upper gastrointestinal tract under fasting and fed conditions using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME)^® platform. Capsules contained caffeine as a marker of capsule dissolution, and pancreatin as an active ingredient for which activity was determined by the conversion of tributyrin. Readouts included visual capsule scoring, the analysis of caffeine release, and the quantification of tributyrin-to-butyrate conversion at the end of each gastrointestinal tract segment. Results: The single VCP capsules had a high level of caffeine release at the end of the stomach incubation with low butyrate recovery (16-21%), suggesting the rapid release and gastric degradation of the unprotected enzyme. The single DR, DR-in-VCP, and VCP-in-DR formulations showed caffeine release at the end of the duodenum and/or jejunum and had high butyrate recovery, ranging from 53% to 87%. The DR-in-DR formulation had the most delayed release, with incomplete caffeine release and low-to-moderate butyrate recovery (10-36%). Conclusions: Fast capsule dissolution led to the reduced enzymatic activity of the active ingredient, while delayed dissolution resulted in inadequate time for the enzymatic conversion of tributyrin to butyrate. These results highlight that capsule selection should align with the intended use and targeted nutrient delivery, with DUOCAP^® formulations being best suited for small intestinal (VCP-in-DR and DR-in-VCP) and colonic (DR-in-DR) delivery.