In vitro evaluation of the gastrointestinal delivery of acid-sensitive pancrelipase in a next generation enteric capsule using an exocrine pancreatic insufficiency disease model.

ABSTRACT

The dissolution characteristics of five capsules (Next Generation Enteric [NGE], Vcaps® Enteric [VCE], VCE DUOCAP® [VCE/VCE] system, Hard Gelatin Capsule [HGC] as negative control, and Creon® 10,000 U as market reference) were evaluated using an in vitro simulation of the stomach and upper intestinal tract with an acidic duodenal incubation (pH 4.5 for the first 10 min, pH 6 for the remaining 17 min) to simulate exocrine pancreatic insufficiency. Caffeine was a marker of capsule dissolution, and tributyrin to butyrate conversion measured pancrelipase activity. All capsules were filled with pancrelipase; the NGE, VCE, VCE/VCE, and HGC capsules also contained 50 mg caffeine. Caffeine was released first from the HGC capsule, followed by the VCE, NGE, and VCE/VCE capsules. Pancrelipase activity followed this trend and demonstrated a similar activity level over time for the NGE, VCE/VCE, and Creon® capsules. The HGC formulation confirmed gastric degradation of unprotected pancrelipase. NGE capsules provided similar protection to the simple fill formulation as observed for the complex formulation of the Creon® capsule in a setting with increased pepsin activity and may hasten the time needed to go from formula development to first-in-human studies for pH sensitive drugs or those requiring small intestine targeting.