Optimization of the preparation conditions of thermo-sensitive chitosan hydrogel in heterogeneous reaction using response surface methodology.

A thermo-sensitive hydroxybutyl chitosan (HBC) hydrogel was prepared by using 1,2‑butene oxide as an etherification modifying agent. To obtain the maximum yield of HBC, response surface methodology (RSM) was applied to optimize its preparation conditions. Key factors were chosen firstly by Plackett-Burman design (PBD) experiments, such as the concentration of NaOH, the ratio of isopropanol to water and reaction temperature. Steepest ascent experiments were employed to reach the top region of the response and determine the appropriate levels of three key factors. A three-level-three-variable Box-Behnken design (BBD) was used to further optimize the synthesis parameters. The results indicated that when the concentration of NaOH and the ratio of isopropyl alcohol to water were 40.65% and 2.68:1 at reaction temperature of 59 °C, respectively, the yield of HBC production was 5.897 ± 0.112 g and close to the predicted value (6.002 g), which demonstrated that the effectiveness of BBD model and the controllability for the yield of HBC in the heterogeneous reaction system.