The objective of this study was to investigate the use of Raman spectroscopy for the quantitative and qualitative analysis of an active ingredient in hot-melt extruded film formulations. Clotrimazole and ketoprofen were used as the active pharmaceutical ingredients (APIs) in the subject formulations. Films were prepared with contents varying from 1 to 20% of the respective API. Raman spectroscopy was used to quantify these APIs, both off-line and on-line. The spectral data were also used to ascertain the physical status of these APIs in the formulations. For off-line analysis, the films were cut into small rectangles, and the amount of the API was measured using a fiber optic probe equipped with a non-contact optic (NCO). For on-line analysis, real-time measurements were accomplished by fixing the probe over the extruded film for continuous data collection. Raman spectroscopy can be a convenient alternative to HPLC and other techniques currently employed for the quantification of the API in these formulations. Because Raman is also sensitive to changes in crystallinity, employment of the technique provided additional information to deduce the crystalline status of the API. The results reported in this paper suggest the suitability of Raman for PAT applications because of the on-line capability.