Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide.pdf

International Journal of Pharmaceutics 324 (2006) 103–115 Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine Sunil A. Agnihotri, Tejraj M. Aminabhavi ∗ Drug Delivery Division, Center of Excellence in Polymer Science, Karnatak University, Dharwad 580 003, India Received 30 November 2005; received in revised form 3 April 2006; accepted 28 May 2006 Available online 3 June 2006 Abstract This paper describes the synthesis of capecitabine-loaded semi-interpenetrating network hydrogel microspheres of chitosan-poly(ethylene oxide- g-acrylamide) by emulsion crosslinking using glutaraldehyde. Poly(ethylene oxide) was grafted with polyacrylamide by free radical polymerization using ceric ammonium nitrate as a redox initiator. Capecitabine, an anticancer drug, was successfully loaded into microspheres by changing experimental variables such as grafting ratio of the graft copolymer, ratio of the graft copolymer to chitosan, amount of crosslinking agent and percentage of drug loading in order to optimize process variables on drug encapsulation efficiency, release rates, size and morphology of the microspheres. A 24 full factorial design was employed to evaluate the combined effect of selected independent variables on percentage of drug release at 5 h (response). Regression models were used for the response and data were compared statistically using the analysis of variance (ANOVA). Grafting, interpenetrating network formation and chemical stability of the capecitabine after encapsulation into microspheres was confirmed by Fourier infrared spectra (FTIR). Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) stu