Pectin Film Coated Pellets for Colon-targeted Delivery of Budesonide: In-vitro/In-vivo Evaluation in Induced Ulcerative Colitis in Rat.

Abstract

The main objective of this study was to prepare colon-specific pellets of budesonide, using pectin as film coating. Pellet cores of budesonide were prepared by extrusion / spheronization technique. Pectin, in different ratios was combined with Eudragit RS30D, Eudragit NE30D or Surelease to produce film coating. The dissolution profiles of pectin coated pellets were investigated in pH of 1.2 (2 h), pH of 7.4 (4 h) and pH of 6.8 in the absence as well as presence of rat cecal contents (18 h). Finally the selected formulation was evaluated on trinitrobenzenesulfonic acid (TNBS) induced ulcerative colitis in rat model, in comparison with conventional UC treatments. The dissolution profiles of pectin coated pellets showed that the release of budesonide in presence of rat cecal content depended on adjuvant polymer, the ratio of pectin to polymer and film thickness. Coated pellets, prepared out of pectin and Surelease at a ratio of 1:3 at coating level of 35% (w/w), could increase budesonide release statistically in presence of rat cecal content, while they released no drug in pH of 1.2 and 7.4. Animal experiments revealed the therapeutic efficacy of pectin/Surelease-coated pellets of budesonide in alleviating the conditions of TNBS-induced colitis model as reflected by weight gain, as well as improvement of clinical, macroscopic and microscopic parameters of induced colitis. This confirmed the ability of the optimized formulation for targeted drug delivery of budesonide to colon.