The present work investigates the preparation and the release of acetaminophen from spray-dried microparticles. Two cellulose derivatives were tested as sustaining agents: microcrystalline cellulose (MCC) and sodium carboxymethylcellulose (NaCMC). In-vitro dissolution studies were carried out in dissolution media of different pH. With MCC, the adsorption of acetaminophen on the surface or in the pores of the polymer does not allow a significant sustained release of the drug, which completely dissolves in 1 h. Conversely, the use of NaCMC retards the release of acetaminophen over a period of 6-8 h. The drug release depends on the plasticizer used and on the pH of the dissolution medium, and the mechanism consists essentially in the diffusion of the drug through the swollen polymeric matrix. The pH dependence observed can be correlated with a lower hydrophylicity of the polymer in acidic medium, which retards gel formation.