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

Up to 50% of Crohn's disease and ulcerative colitis patients suffer from ileo-colonic inflammation. Topically delivered budesonide is an effective treatment but in vitro as well as clinical data suggest that oral formulations currently used in clinical practice are not optimal to treat the ileo-colon. 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. Targeted delivery was achieved by coating the tablets with the ColoPulse technology (ColoPulse 3 mg or ColoPulse 9 mg, respectively). Tablets were tested in a 10-h gastrointestinal simulation system for site-specific release, zero-order release kinetics (R-2 >= 0.950), release rate, and completeness of release (>= 80%). Release profiles of the novel formulations were compared with Entocort, Budenofalk, and Cortiment (budesonide MMX). ColoPulse 3 mg and 9 mg were targeted to the simulated ileo-colon, budesonide release was complete and in a sustained zero-order manner, and both formulations complied with a 6-month accelerated stability study. None of the formulations currently used in clinical practice targeted the ileo-colon. These in vitro results are discussed in light of clinical data. ColoPulse 3 mg and 9 mg are novel interesting formulations for the treatment of the entire ileo-colon in inflammatory bowel disease.