Multidimensional Role of Inulin as Synbiotic, Drug Carrier and Synergistic Adjuvant for the Colonic Delivery of 5-FU

V.      R. Sinha; Honey

Abstract

Natural polysaccharides are being extensively manipulated for the colon drug delivery systems. Nowadays, therapeutic compositions are being investigated that can effectively play a versatile role. The present investigation is aimed to design a colon specific microbially triggered system using biodegradable co-polymer mixtures. The prime focus of the study was to design and evaluate a swelling dependent delayed release system for a colonic delivery of anticancer agent 5-Fluorouracil (5-FU) and further to determine the effects of carboxypolymer (Carbopol®71G-NF) on release behavior of 5-FU from a matrix tablet system containing different amounts of inulin (a biodegradable oligofructose) aiding in enzymatic degradation by colonic microflora. Mixed film coating with a blend of Ethylcellulose: Eudragit®S-100 (2:1) at coat weight levels of 2%w/w, 4%w/w and 6.0%w/w was carried out respectively, which further retarded the drug release in the initial hours of the in-vitro dissolution profile. Swelling studies were also carried out on uncoated matrix tablet batches. The releases studies with or without rat caecal contents were performed on optimized batches and the samples were analyzed by a validated RP-HPLC method. In-vitro rat caecal study results revealed that complete drug release would occur from the tablets in the human colonic microenvironment. The study revealed an effective site specific delivery of a hydrophilic chemotherapeutic agent, 5-FU to the colon for the treatment of various local as well as systemic pathologies.

Keywords: Inulin, 5-FU, colon targeted drug delivery, microbially triggered system, mixed film coating, Colorectal cancer, swelling, Matrix