Mebeverine HCl is a water soluble drug commonly used to treat irritable bowel syndrome by acting directly on the smooth muscles of the colon. This work was aimed at the formulation and in vitro evaluation of a colon-targeted drug delivery system containing mebeverine HCl. Matrix tablets were prepared using ethyl cellulose (EC), Eudragit RL 100 either solely or in combination by wet granulation technique. Dissolution was carried out in 0.1 N HCl for 2?h followed by pH 6.8 phosphate buffer for eight hours. Uncoated forms released more than 5% drug in 0.1 N HCl therefore, Eudragit L100 was used as a coat. The results indicated very slow release profile. As a result, single retardant was used to prepare the matrix and coated by Eudragit L 100. The matrix containing 7% Eudragit RL 100 and 6% of binder was subjected to further studies to assess the effect of different coats (Eudragit L 100-55 and cellulose acetate phthalate) and different binders (pectin and sodium alginate) on the release profile. Eudragit L 100 and pectin were the best coating agent and binder, respectively. The final formula was stable and it can be concluded that the prepared system has the potential to deliver mebeverine HCl in vivo to the colon.
In the present study, L. ferrugineus methanol extract (LFME) was evaluated for its blood pressure lowering effect in anesthetized normotensive Sprague Dawley (SD) rats and its spasmogenic effect in isolated guinea pig ileum. The possible mechanism(s) of action were also investigated. LFME was obtained by Soxhlet extraction. The rats were fasted overnight and anesthetized with sodium pentobarbitone (60 mg/kg i.p.). LFME was administered in i.v. boluses in the concentrations of 25, 50, 100 and 200 mg/kg respectively, with concomitant monitoring of mean arterial pressure (MAP). It was found that LFME dose-dependently reduced MAP. An i.v. bolus injection of atropine significantly decreased the blood pressure lowering effect of LFME. Similarly, L-NAME (Nomega-nitro-L-arginine methyl ester) significantly lowered both the MAP and the action duration. Conversely, no significant change in MAP was seen following i.v. injections of neostigmine, hexamethonium, prazosin and propranolol. LFME also produced a dose-dependent contractile effect in guinea pig ileum. This contraction was significantly reduced in atropine pre-incubated tissue segments, yet it was significantly enhanced in the presence of neostigmine. No appreciable change in the ability of LFME to contract guinea pig ileum was seen in the presence of hexamethonium. Accordingly, it can be postulated that LFME possesses a marked hypotensive effect that can be attributed to stimulation of muscarinic receptors and/or stimulation of nitric oxide (NO) release. Moreover, LFME retains a considerable spasmogenic action due to its cholinergic properties. The hypotensive and spasmogenic effects of LFME justify its traditional uses.