Synthesis and characterisation of inulin-azo hydrogels designed for colon targeting

The present paper describes the synthesis and characterisation of new hydro gel systems designed for colon targeting. The gels were composed of methacr ylated inulin (MA-IN), copolymerized with the aromatic azo agent bis(methac ryloylamino)azobenzene (BMAAB) and 2-hydroxyethyl methacrylate (HEMA) or me thacrylic acid (MA). The gels were assessed by studying the influence of va rious parameters on the dynamic and equilibrium degree of swelling. It was shown that the uptake of water in the gels was inversely proportional to th e MA-IN feed concentration, the degree of substitution of the inulin backbo ne, and the concentration of BMAAB. The latter can probably be explained by the hydrophobic nature and rigidity of the aromatic azo agent. Incorporati on of the hydrophilic monomers HEMA or MA also reduced the equilibrium degr ee of swelling. An increasing network density and hydrogen bonding propensi ty, can suggested to be responsible for this observation. It was shown that water uptake in the hydrogels was controlled by both relaxation and diffus ion mechanisms (anomalous behaviour). When the release of the model drug pr ednisolone was studied in phosphate buffer, it was shown that > 80% of the drug was released during the first 3 h from hydrogels of MA-IN:HEMA. Althou gh drug release decreased significantly from MA-IN:HEMA:BMAAB hydrogels, it remained too high: similar to 50% of the drug was released after 5 h, The same observation was made for hydrogels containing MA instead of HEMA. Thes e results clearly point out the difficulty in finding the optimal balance b etween swelling to allow degradation in the colon (high swelling of the gel s) and low premature drug release before the colonic environment is reached (low swelling properties). (C) 2001 Elsevier Science B.V. All rights reser ved.