Abstract
Objective: Mebeverine hydrochloride is an antispasmodic agent that has a direct musculotropic action on the smooth muscles of the gastrointestinal tract; especially the colon.Therefore, the current study aimed at formulating and optimizing colon targeted mebeverine hydrochloride microspheres for treatment of chronic gastrointestinal disorder. Methods: Mebeverine hydrochloride-loaded chitosan microspheres were formulated adopting emulsion cross-linking method using glutaraldehyde as a cross linking agent. A 33 Box Behnken design was utilized in formulating the microspheres and investigating the effect of different formulation factors such as drug: polymer ratio (X-1), stirring speed (X-2) and the surfactant concentration (X-3) on particle size (Y-1), the entrapment efficiency percentage (Y-2) and the cumulative release percentage of mebeverine hydrochloride after 8 h (Y-3). Result: The particle size and entrapment efficiency were significantly affected by tested formulation parameters. The release of mebeverine hydrochloride from optimized formula was pH dependent. In simulated gastric fluid, less than 10% of entrapped mebeverine hydrochloride was released, while, a relatively high amount of the drug (> 65%) was released in simulated colonic fluid (pH 7.4). The in vivo pharmacokinetic study revealed that the optimized formula of microspheres exhibited increased oral absorption of mebeverine hydrochloride, compared to free drug (C-max 168.51 +/- 20.05 ng/ml vs. 126.45 +/- 29.46 ng/ml, respectively). In addition, the optimized formula exerted a remarkably higher systemic bioavailability, compared to the free drug. Conclusion: These results underscore the applicability of cross-linked chitosan microspheres as a promising carrier for colon targeted delivery of mebeverine hydrochloride for treating diseases associated with the colon such as irritable bowel syndrome.