Microbiota-triggered colonic delivery: Robustness of the polysaccharide approach in the fed state in man

Abstract

Polysaccharide-based colonic drug delivery requires that the polysaccharide in question avoids pancreatic digestion but undergoes fermentation by the colonic bacteria. Resistance of such dosage forms to pancreatic enzyme digestion is generally only tested in the fasted state, despite the higher enzymatic challenge in the fed state. Theophylline pellets coated with a polysaccharide-based (amylose) colon-specific film were administered to seven healthy volunteers (two-way crossover study, fed/fasted). The transit of the pellets through the gut was followed by gamma scintigraphy. The amount of drug released in the gut from the theophylline pellets was calculated after recovering and assaying any intact pellets in the faecal material. Of the drug released, the amount absorbed was measured using plasma profiling. Gastric empyting of pellets was delayed in the fed state, and this translated to a delayed colon arrival time. In both fed and fasted states, there was no drug release in the stomach or small intestine confirming the ability of the amylose in the coating to resist pancreatic digestion despite elevated enzyme levels in the fed state. Drug plasma levels were detected after the pellets arrived in the colon and there was a delayed T_max in the fed state; the mean caecal arrival time in the fasted state was 5.5 ± 1.1 h and the T_max was 9.3 ± 0.5 h, whereas in the fed state the mean caecal arrival time was 6.9 ± 2.1 h and the T_max was 10.3 ± 0.8 h. On average, over 92% of the drug was released in the colon; the remaining was removed in faecal material. Bioavailability was similar (p>0.05) in both feeding states (26.0 ± 6.4 μg h/ml fasted and 24.4 ± 5.1 μg h/ml fed). In conclusion, feeding has no detrimental effects on the behaviour of this polysaccharide-based colonic delivery concept.

Keywords::

• Resistant starch
• amylose
• microflora
• microbiota
• colonic drug delivery
• colonic targeting
• gastrointestinal transit

Declaration of interest: The authors report no conflicts of interest.