Formulation and development of di-dependent microparticulate system for colon-specific drug delivery

Colorectal cancer (CRC) is the third most common cancer globally and the second most common cause of cancer-related deaths. Site-specific delivery of drugs leads to an increase in the availability of drugs at the targeted region. The objective of the present investigation was to develop a dually functional microparticulate colon-targeted drug delivery system of meloxicam for potential application in the prophylaxis of colorectal cancer. Chitosan microspheres were prepared by using emulsification–chemical cross-linking technique. Formulation parameters studied include chitosan concentration, drug to polymer ratio, agitation speed, emulsifier concentration, quantity of cross-linking agent and time for cross-linking. In vitro evaluation of microspheres revealed premature release of drug in the upper part of gastrointestinal tract. Since coating of microspheres is difficult to accomplish (with reproducible results), they were compacted to tablets. Enteric coating of tableted microspheres was achieved using Eudragit® S100. In vitro evaluation and SEM studies depict that the microspheres remain intact during compression process. The developed system was further evaluated for in vivo pharmacokinetic and roentgenography studies. In vivo pharmacokinetic evaluation in rabbits reveal that the onset of drug absorption from the coated tableted microspheres (Tlag time = 4.67 ± 0.58 h) was significantly delayed compared to uncoated tableted microspheres. In vivo roentgenographic study revealed that the system remained intact, until it reaches to the colonic region (5 h). Thus, from the results of the study, it can be revealed that the developed system could serve as a potential tool for efficient delivery of drug to the colonic region.