Development of novel zero-order release budesonide tablets for the treatment of ileo-colonic inflammatory bowel disease and comparison with formulations currently used in clinical practice

BACKGROUND: In patients with inflammatory bowel disease, the terminal ileum and colon is the most affected region. Oral budesonide is an effective treatment but in vitro as well as clinical data suggest that the formulations currently used in clinical practice are suboptimal to treat the entire ileo-colonic region. OBJECTIVE and DESIGN: The aim of this in vitro study was to develop ileo-colonic-targeted zero-order sustained-release tablets containing 3 mg or 9 mg budesonide [ColoPulse 3 mg and 9 mg, respectively). METHODS: Tablets were tested in a 10 hour gastrointestinal simulation system for site-specific release, zero-order release kinetics [R2 ≥ 0.95], release rate, and completeness of release [≥ 80%]. Release profiles of the novel formulations were compared with Entocort, Budenofalk, and Cortiment (budesonide MMX). RESULTS: None of these formulations currently used in clinical practice targeted the entire ileo-colonic region. However, ColoPulse 3 mg and 9 mg were targeted to the ileum, released the entire dose with zero-order release kinetics in the ileo-colonic region, and complied with a 6-month accelerated stability study. CONCLUSION: Therefore, ColoPulse 3 mg and 9 mg are novel, interesting formulations for the treatment of the entire ileo-colonic region in inflammatory bowel disease.