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.
RCT Entities:
AIMS: To study the delivery of 15 mg beclomethasone17,21-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.
Authors: C J Mulder; E Endert; H van der Heide; H J Houthoff; W Wiersinga; E H Wiltink; G N Tytgat Journal: Neth J Med Date: 1989-08 Impact factor: 1.422