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

Turbidimetric titration revealed that there were electrostatic attractive i nteractions between citrate and chitosan in the pH region of 4.3-7.6, depen ding;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 him was sensitive to pH, ionic strength etc. Under acidic conditions, citrate/chitosan film swelled and even dissoc iated in the pH less than 3.5, and the model drugs (brilliant blue and ribo flavin) incorporated in the film were released quickly (usually within 2 h released completely in simulated gastric fluid at 37 degreesC) while under neutral conditions the swelling ratio of citrate/chitosan film was less Sig nificant and the release rate of brilliant blue and riboflavin was low (les s than 40% released in simulated intestinal fluid in 24 h). Sodium chloride weakened the electrostatic interaction between citrate and chitosan, and t herefore facilitated the film swelling and accelerated drug release. The pa rameters of film preparation such as citrate concentration, solution pH etc . influencing the film swelling and drug release profiles were examined. Th e lower concentration and the higher pH of citrate solution resulted in a l arger swelling ratio and quicker riboflavin release. To improve the drug co ntrolled release properties of citrate/chitosan film, heparin, pectin and a lginate were further coated on the film surface. Among them only the coatin g of alginate prolonged riboflavin release noticeably (for 80% of drug rele ased 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 del ivery such as for the site-specific drug controlled release in stomach. (C) 2001 Elsevier Science B.V. All rights reserved.