The aim of this study was to investigate the solubility of mefenamic acid (MA), a highly cohesive, poorly water-soluble drug in a copolymer of polyoxyethylenepolyoxypropylene (Lutrol F68 1 ), and to understand the effect drug polymer solubility has on in vitro dissolution of MA. Solid dispersions (SD) of MA were prepared by a hot melt method, using Lutrol F68 1 as a thermoplastic polymeric platform. High-speed differential scanning calorimetry (Hyper-DSC), Raman spectroscopy, powder X-ray diffractometry (PXRD) and hot-stage/fluorescence microscopy were used to assess the solubility of the drug in molten and solid polymer. Drug dissolution studies were subsequently conducted on single-phase solid solutions and biphasic SD using phosphate buffer pH 6.8 as dissolution media. Solubility investigations using Hyper-DSC, Raman spectroscopy and hot-stage microscopy suggested MA was soluble in molten Lutrol F68 1 up to a concentration of 35% (w/w). Conversely, the solubility in the solidstate matrix was limited to <15% (w/w); determined by Raman spectroscopy, PXRD and fluorescence microscopy. As expected the dissolution properties of MA were significantly influenced by the solubility of the drug in the polymer matrix. At a concentration of 10% (w/w) MA (a single phase solid solution) dissolution of MA in phosphate buffer 6.8 was rapid, whereas at a concentration of 50% (w/w) MA (biphasic SD) dissolution was significantly slower. This study has clearly demonstrated the complexity of drugpolymer binary blends and in particular defining the solubility of a drug within a polymeric platform. Moreover, this investigation has demonstrated the significant effect drug solubility within a polymeric matrix has upon the in vitro dissolution properties of solid polymer/drug binary blends.