Design, Development, and Characterization of Imiquimod-loaded Chitosan Films

Abstract

Basal Cell Carcinoma (BCC) is a common malignant tumor in Caucasians and accounts for 95% of non-melanoma skin cancers in the United States. BCC is primarily caused by UV radiation and is slow growing, although if left untreated, has high potential for spread to surrounding tissues. Non-surgical treatment of superficial BCC involves the use of AldaraTM cream containing 5% w/w imiquimod as the active ingredient. Imiquimod (AldaraTM), a Toll-like receptor (TLR) agonist, is an immune response modifier with potent indirect antiviral activity. The topical delivery of imiquimod is desired over oral administration to eliminate the first-pass metabolism of drug in the liver while maximizing the drug concentration at the affected area. However, cream dosage form suffers from the disadvantages such as dose variability, poor drug availability due to incomplete release of the drug and poor patient compliance. We hypothesized that the sustained release of a therapeutic dose of imiquimod from the film would result in an effective treatment, while eliminating the need for daily cream application and the dosing variations associated with it. In order to test this hypothesis, imiquimod containing chitosan films were manufactured to achieve the desired controlled delivery of imiquimod and characterized for drug physical form, drug loading, content uniformity, and release behavior. In addition, effect of varying concentrations of Imiquimod and molecular weight of chitosan was studied on the release characteristics of the film. In-house HPLC method was developed to analyze the drug concentrations during the release studies. The X-ray diffraction (XRD) data and content uniformity studies demonstrated the uniform imiquimod loading with no change in the physical form of the API within the chitosan film matrix. In conclusion, chitosan films containing imiquimod were developed with desired rate and extent of delivery of Imiquimod for single use weekly.