Sustained release nanospheres were prepared from the polymethacrylates Eudragit(R) S 100 and E 100 containing a water insoluble dye by a salting-out method. Coumarin-6 was used as a model for insoluble analgesics to ascertain uptake and release properties dependent on polymer characteristics and pH. Morphology and particle size were characterized by scanning electron microscopy (SEM). Particles were smooth, spherical and uniform with diameters ranging from 0.6-0.8 mum. Yield was 38% and 86% for E 100 and S 100 , respectively, and encapsulation of coumarin-6 efficiency was 58% and 75%, respectively. Coumarin-6 was stable within the polymer matrix at temperatures from -20degreesC to 45degreesC for 4 months. Release was most efficient from S 100 polymers in phosphate buffer at pH 7.4 and 8.0 reaching a maximum 5 hours prior to samples at pH 7.0 and 9.0. Release was biphasic and concentration as a function of the square root of time produced linear data suggesting a Higuchi type diffusion from a polymer matrix. Release from E 100 was 65% lower than that from S 100 and was not solely dependent upon the ionization of polymer but most likely due to a combination of factors including buffer ionization.