The Effect of Polymer Molecular Weight on Citrate Crosslinked Chitosan Films for Site-Specific Delivery of a Non-Polar Drug

Purpose: To develop citrate crosslinked chitosan films using chitosan of different molecular weights (MW) in order to achieve site-specific delivery of a model non-polar drug, indomethacin. Methods: Films prepared with different molecular weights of chitosan and incorporating indomethacin as a non-polar model drug were obtained by a casting/solvent evaporation method. The chitosan films were crosslinked by dipping in varying concentrations of sodium citrate solution and for different crosslinking times. The films were assessed by, amongst others, scanning electron microscopy (SEM), dissolution studies and differential scanning calorimetry (DSC) for surface morphology, drug release and ingredient compatibility, respectively. Results: Crosslinking time and concentration of crosslinking agent significantly (p < 0.05) influenced the in vitro release of indomethacin as well as swelling of the films. Also, the higher the molecular weight (MW) of chitosan the lower the drug release rate (p < 0.05). Furthermore, film swelling index rose as chitosan MW decreased (p < 0.05). The practical absence of the sharp endothermic peak characteristic of indomethacin in the films suggests that crosslinking may have transformed the drug from the crystalline to the amorphous state. Conclusion: The citrate-crosslinked chitosan films can be modulated to vary swelling and drug release at pH 3.5 and 6.2; this feature makes them useful tools for designing site-specific delivery systems.