The Dual Positive Actions of Colonic Release of Ibuprofen in TNBS-Induced Colitis Wistar Rats

Ibuprofen is a relatively safe anti inflammatory drug among other NSAIDs. However, frequent and long-term administration of ibuprofen in conventional oral preparation is still considered for ulceration. As previously reported, the daily administration of the ibuprofen orally for 14 days in rats caused the gastroduodenal ulcer. Several mechanisms have been reported: the suppression of the gastric prostaglandin synthesis and the local irritant effect on epithelium due to the direct contact of drug with mucosal wall. In this work, developed ibuprofen pellet with double coatings aimed to release ibuprofen only when reaching colonic compartment. The results of pharmacokinetic study reported previously suggested that this might be a successful target. Present study described the potential benefits of this formula in exhibiting effective local anti inflammatory action in colon. Male Wistar rats were induced for ulcerative colitis with 2,4,6-trinitrobenzene sulfonic acid. Twenty four hours after induction, treatments were given using either ibuprofen suspension or pellet for 14 days. Ulcerations were observed visually, with gross anatomic and microscopic examinations. Group treated with ibuprofen pellet showed best recovery nearly close to healthy group. Moreover, the group did not develop ulceration in upper part of GIT. Colonic targeted ibuprofen pellet showed most effective local antiinflammatory action and at the same time reduced the ulcer formation in the upper part of GIT.

Investigation of mitigating effect of colon-specific prodrugs of boswellic acid on 2,4,6-trinitrobenzene sulfonic acidinduced colitis in Wistar rats: Design, kinetics and biological evaluation

To develop a colon-targeting bioreversible delivery system for β-boswellic acid (BBA) and explore utility of its prodrugs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.METHODSSynthesis of 4 co-drugs of BBA with essential amino acids was achieved by CDI coupling, followed by their spectral characterization. In vitro kinetics were studied by HPLC in aqueous buffers, homogenates of gastrointestinal tract and fecal matter. In vivo kinetic studies were performed in Wistar rat plasma, urine and feces. The prodrugs were screened in TNBS-induced colitis modeled Wistar rats. Statistical significance was assumed at P < 0.05, P < 0.01, P < 0.001 when compared with disease controls using one-way and two-way ANOVAs.RESULTSProdrugs were stable in 0.05 mol/L HCl buffer (pH 1.2) and stomach homogenates. Negligible hydrolysis was observed in phosphate buffer and intestinal homogenates. Substantial release (55%-72% and 68%-86%) of BBA was achieved in rat fecal matter and homogenates of colon. In vivo studies of BBA with L-tryptophan (BT) authenticated colon-specific release of BBA. But, surprisingly substantial concentration of BBA was seen to reach the systemic circulation due to probable absorption through colonic mucosa. Site-specifically enhanced bioavailability of BBA could be achieved in colon, which resulted in demonstration of significant mitigating effect on TNBS-induced colitis in rats without inducing any adverse effects on stomach, liver and pancreas. Prodrug of BT was found to be 1.7% (P < 0.001) superior than sulfasalazine in reducing the inflammation to colon among all prodrugs tested.CONCLUSIONThe outcome of this study strongly suggests that these prodrugs might have dual applicability to inflammatory bowel disease and chronotherapy of rheumatoid arthritis.