Calcium silicate-reinforced pH-sensitive alginate-gellan gum composite hydrogels for prolonged drug delivery

This study disclosed the synthesis and characterization of externally and/or internally crosslinked alginate-gellan gum composite interpenetrating polymer networks (IPN) and IPN hydrogel microspheres for controlled delivery of gliclazid. The internal cross-linking of the polymer sol was accomplished via slow release of Ca2+ ions from calcium silicate in presence of gluconic acid d-lactone. The microspheres had spherical shape with smooth surface morphology. The IPN or composite IPN hydrogel microspheres had drug entrapment efficiency of 70%-76%. Incorporation of gellan gum or gellan gum/calcium silicate in the alginate sol sustained the release of drug in simulated gastrointestinal fluids over 12 h without any sign of particle disintegration. Inclusion of calcium silicate in alginate gels was ineffective in controlling drug release under simulated gastrointestinal milieu. The drug release obeyed anomalous diffusion mechanism after inclusion of gellan gum or gellan gum-calcium silicate in the alginate gel microspheres. Fourier-transform infrared (FTIR) spectroscopy and zeta analysis confirmed absence of drug-polymer chemical interaction. The thermal and x-ray diffraction analyses suggested that the drug transformed into amorphous state after incorporation into composite hydrogel system. Hence, it may be advantageous to combine internal and external gelation procedures for creating composite IPN or IPN hydrogel microspheres for avoiding burst effect of alginate microspheres and managing desired drug release patterns in vitro.