The purpose of this study was to prepare solid dispersion formulations (SDs) of ketoprofen (KP) in order to increase solubility and dissolution rate. This approach is important because of the potential usage of these formulations for neurodegenerative diseases such as Alzheimer's. SDs of KP in different ratios as drug-polymer system were prepared using melting method and ideal formulation was selected by in vitro and in situ studies. In situ effects of these developed formulations on DNA damage was determined in rat brain cortex homogenates. Our results showed that SDs helped to improve the dissolution rates of KP. These formulations decreased the levels of DNA damage in rat brain cortex when compared to controls. The selected B3 formulation would have a potential protective effect on neurodegenerative processes including inflammation. In addition, cytotoxic potential and long term effect of B3 formulation on cell survival were evaluated via MTT and colony formation assays, respectively. Tested formulation had no cytotoxic effect and did not decrease the cell survival at its pharmacologically relevant and higher concentrations. Overall, newly developed SD formulation of KP is suggested to be a promising candidate for long term use in neurodegenerative diseases because of its improved solubility and dissolution rates, increased beneficial activity against DNA damage and its short and long term safety in cells.