Novel pH-sensitive citrate cross-linked chitosan film for drug controlled release

Abstract

Turbidimetric titration revealed that there were electrostatic attractive interactions between citrate and chitosan in the pH region of 4.3–7.6, depending on their degree of ionization. Citrate cross-linked chitosan film was prepared simply by dipping chitosan film into sodium citrate solution. The swelling ratio of citrate/chitosan film was sensitive to pH, ionic strength etc. Under acidic conditions, citrate/chitosan film swelled and even dissociated in the pH less than 3.5, and the model drugs (brilliant blue and riboflavin) incorporated in the film were released quickly (usually within 2 h released completely in simulated gastric fluid at 37°C) while under neutral conditions the swelling ratio of citrate/chitosan film was less significant and the release rate of brilliant blue and riboflavin was low (less than 40% released in simulated intestinal fluid in 24 h). Sodium chloride weakened the electrostatic interaction between citrate and chitosan, and therefore facilitated the film swelling and accelerated drug release. The parameters of film preparation such as citrate concentration, solution pH etc. influencing the film swelling and drug release profiles were examined. The lower concentration and the higher pH of citrate solution resulted in a larger swelling ratio and quicker riboflavin release. To improve the drug controlled release properties of citrate/chitosan film, heparin, pectin and alginate were further coated on the film surface. Among them only the coating of alginate prolonged riboflavin release noticeably (for 80% of drug released the time was extended from 1.5 to 3.5 h with 0.5% w/v alginate used). The results indicated that the citrate/chitosan film was useful in drug delivery such as for the site-specific drug controlled release in stomach.