Novel Enteric Microsphere of Beclomethasone Dipropionate With Colon Delivery and Enhancement of Anti-Inflammatory Effects

Abstract

The present study aimed to develop a novel colon-targeting microsphere of beclomethasone dipropionate (cMS/BDP) with enhanced pharmacological effect of BDP in the colon. cMS/BDP was prepared using Eudragit^® S-100 by the emulsion solvent diffusion method, and its physicochemical properties were characterized. A pharmacokinetic study was conducted to assess systemic exposure and colon distribution of BDP after oral administration of cMS/BDP to rats. A pharmacodynamic study was carried out to evaluate the anti-inflammatory effect of cMS/BDP after its oral administration to ulcerative colitis model rats. The particle size of cMS/BDP was calculated to be ca. 20 μm, and most BDP in cMS/BDP might be in an amorphous state. In dissolution tests, cMS/BDP showed pH-dependent release behavior of BDP and marked BDP release at pH 7.4. After oral administration of cMS/BDP (5 mg-BDP/kg) to rats, BDP was rapidly metabolized to beclomethasone 17-monopropionate (17-BMP, a BDP metabolite) in the gastrointestinal tract and liver, and relative oral bioavailability of 17-BMP in the cMS/BDP group was calculated to be ca. 4.8% compared with that in the BDP solution group. The tissue-to-plasma partition coefficient value, an index of colon distribution, for cMS/BDP was found to be 15-fold higher than that for BDP solution. In the cMS/BDP (50 μg/kg) group, colonic myeloperoxidase activity and hyperplasia of the submucosa were negligibly elevated. From these findings, the cMS approach for BDP would be a promising dosage option for strategic colon delivery, leading to an improved therapeutic potential of BDP with a wide safety margin.