Nonsteroidal anti-inflammatory drugs (NSAIDs) were successfully used for the alleviation of pain, fever and inflammation for at least 3500 years and continue to be used daily by millions of patients worldwide. NSAIDs are widely used for the treatment of musculoskeletal disorders such as osteoarthritis and rheumatoid arthritis. Dexketoprofen trometamol (DT) is the dextrorotatory enantiomer of ketoprofen formulated as the tromethamine salt. DT’s distribution and elimination half-lives are 0.35 and 1.65 hrs, respectively. Eudragit polymers which are acrylic/metacrylic acid esters act as polyelectrolytes regulated by percentage of cationic (quaternary ammonium) and non-ionized (ether) groups in their structures. Some of them can be considered as polycations (Eudragit type E, RL, RS and NE) and the others as polyanions (Eudragit types L and S). Eudragit RL100 is a well-known polymer commonly used as a pharmaceutical excipient for enteric and controlled-release dosage forms. Over the past few decades, there was considerable interest in developing biodegredable nanoparticles as effective drug delivery systems. Preparing and characterizing polymeric nanoparticles for oral controlled analgesic delivery was aimed in this study. Spray-drying was used as the preparation method and characterization was achieved by particle size/PDI and zeta potential measurements, DCS thermograms, SEM imaging and FT-IR and NMR spectroscopic analyses.