Synthesis and characterization of polyacrylamide-grafted chitosan hydrogel microspheres for the controlled release of indomethacin

Microspheres of polyacrylamide-grafted-chitosan crosslinked with glutaraldehyde were prepared and used to encapsulate indomethacin, a nonsteroidal anti-inflammatory drug. The microspheres were produced by the water/oil emulsion technique and encapsulation of indomethacin was carried out before crosslinking of the matrix. The extent of crosslinking was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry. Microspheres were characterized for drug-entrapment efficiency, particle size, and water transport into the polymeric matrix as well as for drug-release kinetics. Scanning electron microscopy confirmed the spherical nature and surface morphology of the particles with a mean particle size of 525 gm. Dynamic swelling experiments suggested that, with an increase in crosslinking, the transport mechanism changed from Fickian to non-Fickian. The release of indomethacin depends upon the crosslinking of the network and also on the amount of drug loading. This was further supported by the calculation of drug-diffusion coefficients using the initial time approximation. The drug release in all the formulations followed a non-Fickian trend and the diffusion was relaxation-controlled. (C) 2002 Wiley Periodicals, Inc.