Murat İnal

Controlled release of indomethacin from crosslinked alginate beads

Abstract Beads of the sodium alginate (NaAlg) were prepared by dropping aqueous sodium alginate (NaAlg) into glutaraldehyde (GA) as a crosslinker and HCl as a catalyst mixture solution. Beads prepared were used to deliver a model non-steroid, anti-inflammatory drug, indomethacin (IM). The beads were characterized with Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Chemical stability of the IM after encapsulation into beads was confirmed by FTIR. SEM photograph indicated that alginate bead has spherical shape and rough surface. Preparation conditions of the beads were optimized by considering the percentage of entrapment efficiency, swelling capacity of the beads, particle size and their release data. In vitro release studies were performed in simulated gastric fluid (pH 1.2) for the initial 2 h, followed by simulated intestinal fluid (pH 7.4) for 4 h. Effects of variables such as, GA concentration, exposure time to GA, drug/polymer (d/p) ratio and percentage of HCl on the release of the IM were investigated. It was observed that, IM release from the beads decreased with increasing GA concentration, exposure time to GA, d/p ratio and percentage of HCl. The highest cumulative IM release obtained at the end of 6 h was 68% for alginate beads which were prepared with 0.5% HCl. On the other hand the least cumulative IM release obtained was to be 20 % for alginate beads which were prepared with 30 min exposure time to GA. In order to understand the crosslinking of the polymeric matrix, the molar mass between crosslinks were calculated using the swelling parameters. It was also found from the swelling experiments that swelling degree of the beads increases with increase in the temperature. The release data have been fitted to an empirical equation to estimate the kinetic parameters. The diffusion coefficient was also calculated for the transport of the drug through the polymeric beads. Values of these parameters were found to be consistent with the release data.