Effect of molecular weight and degree of deacetylation on controlled release of isoniazid from chitosan microspheres

Glutaraldehyde cross-linked chitosan microspheres for controlled release of isoniazid were prepared using chitosan of different molecular weights (MWs) and degrees of deacetylation (DDAs). Chitosan microspheres were characterized for their size, hydrophobocity, degree of swelling and loading of isoniazid. Hydrophobicity of chitosan microspheres increased on increasing the degree of cross-linking and MW of chitosan. Chitosan microspheres with high degree of deacetylation (DDA) (75 wt%), high MW chitosan (2227 kg mol(-1)), and with 12 wt% concentration of glutaraldehyde showed optimum loading and release of isoniazid. The isoniazid from chitosan microspheres was released in two steps, i.e. burst (%R-B) and controlled (%R-C) steps. The microspheres with low MW chitosan (260 kg mol-1) and low DDA (48 wt%) showed prominent burst release of isoniazid, but microspheres with high MW chitosan (2227 kg mol(-1)) and high DDA (75 wt%) have released more isoniazid in a controlled manner (60 wt%) at 37 degrees C in a solution of pH 5.0 +/- 0.1. The burst step of drug release (%R-B) has followed first order kinetics, whereas controlled step of drug release (%R-C) followed zero order kinetics. The burst step of drug release was Fickian and controlled step was non-Fickian in nature. The diffusion constant (D) for isoniazid release was influenced by the properties of chitosan and degree of cross-linking. Copyright (c) 2007 John Wiley & Sons, Ltd.