Fabrication and Evaluations of Dual Crosslinked Mesalamine containing Pectin-Chitosan gel micro beads for controlled and targeted colon delivery

Abstract

Objectives: The aim of the present work was to prepare and characterize mesalamine loaded microbeads (MLM) consisting of optimized ratios of chitosan and pectin polysaccharides using ionic gelation technique for management of inflammatory bowel disease. Methodology: Mesalamine loaded microbeads were prepared using ionotropic gelation method that was double cross linked with calcium chloride (3-6%, w/v) and sodium sulphate (2-4%, w/v) solutions. The formulation was optimized with the help of two levels and three factors factorial design method. The optimization parameters selected for formulation variables were viz., pectin-chitosan ratio, calcium chloride-sodium sulphate ratio and curing time. The prepared formulations were further characterized on the basis of particle size, shape, swelling index, entrapment efficiency, and percentage yield and in vitro drug release studies. The in vitro release studies using rat caecal content (2 and 4 % w/v) was also performed to simulate the human colonic condition. Results: The mean particle size, entrapment efficiency and percentage yield of MLM were ranged from 875.45 to 975.45 µm, 72.2 to 86.7% and 93.6 to 97.9% respectively. The swelling index of MLM formulations revealed lesser into acidic medium, while augmented swellings were found to be at pH 6.8 and 7.2 respectively. The swelling degree was found to be 7.34 to 13.88% into SIF at pH 6.8 whereas, intensely swelled was 16.24 to 46.02% into SCF at pH 7.2 during 8 h studies. In vitro drug release profile of MLM exhibited that only 1.28 to 4.42 drug was released at simulated gastric fluid (SGF, pH 1.2, 2 h), however optimum drug released was found into simulated intestinal fluid (SIF, pH 6.8, 3 h) i.e. 5.33 to 31.33% and into simulated colonic fluid (SCF, pH 7.2, 18 h) i.e. 32.13 to 87.12% correspondingly. Scanning electron microscopy (SEM) revealed that the microbeads were consisting of semispherical and wrinkled rough surfaces. Further, the rat caecal contents (2 and 4% w/v) release studies confirmed for complete polymeric degradation by colonic enzymes. The release kinetics and mathematical modeling studies carried out for optimized formulation shown that the optimized formulations were of non fickian mechanism (n=0.49 to 0.74) type governed by both diffusion and erosion controlled following Higuchi and Korsemeyer peppas model fittings. Conclusion: It can be concluded from the study that the optimized MLM formulations may be effective for colon targeting and treating inflammatory bowel disease.