Abstract Dissolution of poorly water-soluble active pharmaceutical ingredients (APIs) in polymeric melts plays an important role in the manufacturing of solid dispersions and solid solutions. The understanding of the dissolution is essential for selecting the processing equipment, the operating conditions, and the polymer excipients. The methodology presented in this work for ketoprofen (KTO) and polymer excipients serves as a screening process to select the best API-polymer formulation for hot melt extrusion (HME) to target a specific release profile. KTO dispersion within the polymer was characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and dissolution tests. Thermal characterization shows that a single phase amorphous solid solution (one glass transition temperature [T g ]) was achieved under the HME processing conditions and screw configuration; and with the combination of polymer excipients, an extended release profile of KTO was accomplished, releasing 100% of KTO in 24 h.