The rapid expansion of supercritical solutions (RESS) process was used to produce polymeric microparticles or microspheres loaded with pharmaceuticals for drug delivery applications. Poly(L-lactic acid) (L-PLA), naproxen, and a mixture of naproxen/L-PLA were dissolved in supercritical CO2 and precipitated by the RESS process. Composite particles appear as a naproxen core encapsulated in a polymer coating. The solubility of L-PLA and naproxen/L-PLA has been measured at 333.15 K and pressures ranging from 90 to 200 bar by using a dynamic flow apparatus. The lattice fluid theory of Sanchez and Lacombe was tested for its correlative and predictive capability of modeling these supercritical fluid mixtures. The solubility data are combined with morphology studies to investigate the effects of fluid phase interactions on particle formation using RESS.