The gastrointestinal passage and release of beclomethasone dipropionate from oral delivery systems in ileostomy volunteers

Aims To study the delivery of 15 mg beclomethasone 17,21-dipropionate (BDP) to the distal part of the small bowel for three oral sustained-release formulations (I-III) and a reference capsule in volunteer ileostomists, and to compare these findings with the in vitro dissolution profiles. Methods Two groups of nine ileostomy volunteers (aged 20–61 years), who were otherwise healthy, were enrolled in the study. The recovery of BDP and its metabolite beclomethasone 17-monopropionate (B17P) in ileostomy effluent was investigated in a cross-over study after administration of formulations I or II or a reference capsule containing micronised BDP, and in a second open study after administration of formulation III. Radio-opaque granules were coadministered for evaluation of gastrointestinal passage. Ileostomy effluents were collected hourly for 10–12 h following drug intake. After marker beads had been counted on X-rays, ileostomy collections were analysed for BDP and its metabolites. Cumulative recovery, lag-time and mean transit time were determined for drug and marker beads. Results Gastrointestinal passage characteristics were similar for all treatments. Total drug recovery was approximately three times higher for the sustained-release formulations than for the reference capsule. Recovery of B17P from stoma fluid samples was significantly lower for formulation III than for formulations I and II. Conclusions The novel oral formulations delivered substantial amounts of steroid drug at the distal small bowel/proximal colon, which may warrant further studies to evaluate clinical applicability.