Controlled release of sulfasalazine loaded amidated pectin microparticles through Eudragit S 100 coated capsule for management of inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a common colonic disorder affecting most of the world population. In order to overcome the IBD, present study was aimed to fabricate the sulfasalazine loaded amidated pectin microparticles by ionic gelation technique. The microparticles were filled in Eudragit S 100 coated hard gelatin capsules for pH and time dependent drug delivery to the colon especially for the treatment of IBD. The effects of variables such as concentration of crosslinking agent (calcium chloride) and amidated pectin-sulfasalazine ratio were optimized through the particle size, zeta potential, % yield, encapsulation efficiency (% EE), swelling index and in vitro drug release. The optimized formulation, F4 exhibited average particle size (463.33 ± 6.72 μm), zeta potential (−32.10 ± 0.80 mV), yield (91.62 ± 1.97%) and EE (95.62 ± 1.21%). The significant swelling index, 0.88 ± 0.02 θ and 0.98 ± 0.03 θ was achieved with F4 at pH 6.8 and pH 7.4 respectively. The F4 showed maximum drug release (91.12 ± 5.11%) in simulated colonic fluid (SCF, pH 7.4) and 98.07 ± 3.92% (P < 0.05) in rat cecal content (RCC, pH 7.4) for 24 h in a sustained manner. It may be due to the drug released through polymer by diffusion-matrix erosion and bacterial degradation of the microparticles. The F4 formulation displayed non-Fickian pattern of drug release. In vivo study in rabbits confirmed that the enteric polymer coated capsule dissolve at colonic pH 7.4 to release the drug from microparticles. The F4 exhibited remarkable stability at room temperature and shelf-life was found to be 3.3 years. Thus, the sulfasalazine loaded amidated pectin microparticles filled in Eudragit S 100 coated hard gelatin capsule was found to be a potential delivery system for management of IBD.