Chitosan-chondroitin composite films: Comparison with in vitro skin permeation data of hydrophilic and lipophilic drugs

Preformulation studies on transdermal dosage forms involve liberal use of animal skin for assessing the permeation characteristics of drugs, influence of permeation enhancers, optimizing the formulation variables etc. The restricted availability of animal skin due to concerns regarding prevention of cruelty to animals has generated considerable interest in developing polymeric films for use as skin substitute during in vitro permeation experiments. The present investigation aimed at preparing films containing different ratios of chitosan (CH) to chondroitin sulphate (CS) and rigidizing them by dipping in sodium tripolyphosphate (NaTPP) solution. Statistical optimization designs were employed to screen and optimize the active process and formulation variables that significantly influenced the in vitro permeation of 5-fluorouracil (5-FU) and indomethacin (INDO), model polar and non-polar drugs, respectively, across these polyelectric composite (PEC) films. CH to CS ratio, concentration of NaTPP and rigidization time was found to significantly influence the in vitro permeation of both drugs. The presence of both sulfonate and phosphonate linkages in PEC films rigidized by 2% w/v NaTPP allowed lowest permeation of either drug. However, films rigidized by 2.5% w/v NaTPP retained predominantly phosphonate linkages and were highly permeable to both drugs. The in vitro permeation of both drugs across optimized film formulations was not found to be significantly (p<0.05) different as compared to that across rat, rabbit and human epidermal sheets. The optimized PEC films have a great potential to be developed as substitute of animal and human cadaver epidermal sheets for preliminary in vitro permeation studies.