Optimization on preparation conditions of calcium-crosslinked modified chitosan as potential matrix material for theophylline sustained-release beads and its evaluation of release kinetics

Abstract

This study aimed to prepare theophylline loaded hydroxamated chitosan alpha-ketoglutaric acid (HKCTS) microspheres by ion crosslinking method, and optimize the process and formulation variables using response surface methodology. The independent variables studied were pH value, concentrations of Ca(Ⅱ) ion and HKCTS/theophylline ratio. The dependent variables (responses) were drug loading content and encapsulation efficiency. Mathematical equations and response surface plots were used to relate the independent and dependent variables. The release kinetics was evaluated by fitting the experimental data to standard release equations (zero-, first- and Higuchi equation). Results showed that the optimal conditions for microsphere formulation were 9.6 mg/mL Ca(Ⅱ)ion, 1:1 (g/g) HKCTS/theophylline ratio and pH 9.1, the drug loading content and encapsulation efficiency were 53.40% and 69.61%, respectively. The best fit was found with Higuchi model for the microspheres. The response surface methodology could provide a promising application for calcium cross-linked modified chitosan beads as a new matrix for controlled release of theophylline.