Development of Oral Colon Targeted Drug Delivery Systems for Treatment of Inflammatory Bowel Disease Characterization and Evaluation

Abstract

xv newlineAbstract newlineInflammatory bowel diseases (IBDs) are a group of debilitating inflammatory disorders specially newlineinfluencing colonic tissue in which full long term remission with current standardized treatments newlineis yet unidentifiable. The present work was aimed to develop and characterize (in-vitro and invivo) newlinemicrospheres for colon-specific drug delivery. Curcumin and Flurbiprofen were selected newlinefor the present investigation. Curcumin-Zn(II) complex was prepared in a view to increase the newlinesolubility and stability of curcumin, which was characterized by thin layer chromatography, UV newlinespectroscopy, IR spectroscopy and NMR spectroscopy. Chitosan microspheres loaded with newlineCurcumin, Curcumin-Zn(II) and Flurbiprofen were prepared by emulsion cross-linking method, newlinewhich were further coated with Eudragit S-100 by emulsification-solvent evaporation method. newlineThe developed microspheres were characterized in terms of particle size, shape, entrapment newlineefficiency, drug loading, % yield, swelling index, X-ray, in-vitro drug release and release newlinekinetics. The developed microspheres showed uniform spherical shape along with high newlineentrapment efficiency and X-ray diffractogram revealed less intense peaks as compared to free newlinedrug confirming inclusion of drug within microspheres. Uncoated microspheres exhibited burst newlinerelease in initial 4 h while microspheres coated with Eudragit S-100 prevented premature release newlineof drug and showed controlled release up to 12 h following Higuchi model. Based on pattern of newlinedrug release, best formulation of Curcumin-Zn(II) and Flurbiprofen was further investigated for newlinein-vivo studies using acetic acid induced colitis model and for in-vivo organ bio-distribution newlinestudy. In-vivo organ bio-distribution study showed negligible amount of drug in stomach and newlinesmall intestine confirming integrity of microsphere in upper GIT. Ulcer index for Control group newline(83.20±4.72), Curcumin-Zn(II) treated group (63.33±3.78), Curcumin-Zn(II) microspheres newlinetreated group (43.33±4.04), Flurbiprofen treated group (53.33±3.55), Flurbiprofen mi