Application of simultaneous multiple response optimization in the preparation of thermosensitive chitosan/glycerophosphate hydrogels

Abstract

The parameters affecting the sol/gel transition of chitosan-based thermogelling systems, their final proper-ties and structure have been reported. Nevertheless, equa-tions that define this relationship specific for a particular case have not been developed. The aim of this study was to develop these equations for a general formulation without drugs, so they could be used in the preparation of different drug delivery systems. First, a factorial design was built to evaluate the main factors affecting the pH of a gel-forming solution, gelling time at ambient temperature and 37.5 °C and residual mass after exposure to a buffer solution. The analyzed independent factors were: chitosan concentration, β-glycerophosphate concentration, mixing temperature and mixing time. Mixing time was the only factor whose effect on the responses was not significant; the other three factors were considered for the optimization study. Then, a central composite design based on response surface methodology was carried out to develop statistical models which describe the relationship between active independent factors and the studied responses. The optimized gel was prepared and characterized. FTIR experiments showed that hydrogen bonds and electrostatic attraction were the main types of interactions following sol-to-gel transition. The most important finding of this investigation was that the resulting equations could be used to prepare gel-forming solutions with the desired pH, gelling time and residualmass. The significance of these equations was considered in their potential use to design hydrogels intended for con-trolled drug delivery.