Development and Optimization of Macroparticles of Rifaximin for Colon Targeting

Abstract

Objectives: This study is focused to design a colon specific pellet formulation based on the combined use of time-dependent and pH sensitive delivery system using Quality-by-Design (QbD) approach for better and promising treatment of inflammatory bowel disease (IBD).

Materials and Methods: An extrusion-spheronization process was utilized for production of core pellets using ethyl cellulose (EC) as matrix former and microcrystalline cellulose (MCC) as a spheronizing aid. Two critical process parameters (CPPs) i.e., spheronization time and spheronizer speed were taken as independent factors while aspect ratio, sphericity, carr's index, and particle size were taken as dependent responses to optimize the composition of the core pellets. To regulate the drug release, core pellets were coated with Eudragit NE40D and Eudragit FS30D to impart time-dependent and pH sensitive release of drug.

Results: The optimized coated pellets were characterized for concentration of drug and release of drug from the formulation in vitro in different pH media of stomach and intestine. The coating level of the inner and outer polymers was further optimized for the time required for 10 %, 50 % and 90 % drug release. The invitro release profile of the coated pellets depicted the prolonged release of rifaximin. When exposed to Scanning Electron Microscopy the images of coated pellets suggested a uniform and smooth coat of polymers over the surface of pellets.

Conclusion: The formulation in this research work is intended for specific targeting of drug to treat inflammation and owing to this the dose and the associated side effect reduces. This is how it may be better option in comparison to tablets. The result indicates that the developed formulation may possibly reduce the dosing frequency and side effects associated with the conventional tablet formulation for the site-specific targeting at inflammation site.