Sodium citrate cross-linked chitosan films: optimization as substitute for human/rat/rabbit epidermal sheets

PURPOSE. To prepare chitosan films that shall be capable of simulating in vitro permeation of polar (5-FU) and non polar (indomethacin) drugs across rat/rabbit/human epidermis.

Statistical designs were utilized to identify the formulation and process variables that significantly influenced permeation of both drugs across chitosan films cross-linked with sodium citrate (Nacit). In addition, atomic absorption spectroscopy for Na+ and differential scanning calorimetry of these films were performed for understanding the cross-linking behaviour.

Concentration of chitosan, cross-linking time and concentration of cross-linking agent significantly influenced the in vitro flux of both drugs. Na+ content in films cross-linked with Nacit solutions without adjustment of pH was found to increase whereas, DeltaH of cross-linking endothermic transition decreased. However, after dipping these films in phosphate buffer (pH 7.4) both Na+ and DeltaH was found to decrease. Such a decrease was not observed when films cross-linked with sodium citrate solutions after adjustment to pH 5 were dipped in phosphate buffer (pH 7.4). The in vitro permeation of both drugs across latter films was significantly less.

Adjustment of Nacit solution pH to 5 produced ionic complexes that were resistant to alkaline pH. Chitosan films can be cross-linked with Nacit to simulate in vitro permeation of polar and non polar drugs across animal/human epidermis.