The objective of the study was to demonstrate the utility of near-infrared spectroscopy (NIRS) for quantitative analysis of a model drug in hot-melt extruded film formulations. Polyethylene oxide (PEO) films with clotrimazole (CT) as a model drug were prepared by hot-melt extrusion (HME) incorporating drug concentrations ranging from 0-20% and analyzed using a Fourier transform near-infrared (FT-NIR) spectrophotometer in the reflectance mode, High performance liquid chromatography (HPLC) was the reference method used for this study. The NIR calibration model derived for CT was composed of 21 frequency ranges that were correlated to the values quantified using the HPLC reference method. The NIR method developed resulted in an assayed CT amount in the film matrix to be within 3.5% of the quantity determined by the reference method. These studies clearly demonstrate that NIRS is a powerful method for the quantitation of active drug substances contained in films produced by HME and warrants further investigation.