Hot-melt extrusion technology (HME) was used to prepare muco-adhesive matrix films containing 10% w/w clotrimazole (CT) intended for local drug delivery applications for the oral cavity. This study was aimed at the production and characterization of these drug delivery systems for the prophylaxis and treatment of oral candidiasis. The film system's formulation contained hydroxypropyl cellulose and poly(ethylene oxide) as polymeric carriers, the bioadhesive polycarbophil, and other excipients. The CT formulation was processed at a temperature range of 125-130 degrees C utilizing a Killion extruder (Model KLB-100) equipped with a 6-inch flex-lip die. The films were evaluated for postextrusion drug content, physical and chemical content uniformity, drug release, thermal and crystalline behavior, and bioadhesive strength. The extruded films demonstrated excellent content uniformity and a postprocessing drug content of 93.3% (+/- 1.0). The degradation product, (o-chlorophenyl)diphenyl methanol, was also identified and quantitated using high performance liquid chromatography. The films were determined to exhibit desirable and consistent release properties and bioadhesive strength (p < 0.05). The results of this study indicate that HME is a viable technique for the preparation of muco-adhesive films containing clotrimazole for oral candidiasis.