Supercritical fluid technology has recently been proposed in literature to obtain drug controlled release systems as alternative to conventional techniques. In this work, the Supercritical Assisted Atomization (SAA) is proposed to produce hydroxypropyl methylcellulose (HPMC) based composite microparticles using ampicillin trihydrate as model drug. Successful micronization of HPMC alone and, then, coprecipitation of HPMC and ampicillin were obtained using a buffer solution as solvent. Well-defined micrometric particles with spherical or "doughnut-like" morphology were produced in both cases, with a sharp particle size distribution: diameters ranged between about 0.05 and 5.20 mu m. SAA composite microparticles were characterized by differential scanning calorimetry (DSC), Scanning electronic microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) and UV-vis analysis. A solid solution of HPMC and ampicillin was produced; a stabilizing effect of the polymer on the drug was observed, resulting in the protection of ampicillin from thermal degradation. Coprecipitates were produced at different drug/polymer ratios and two kinds of formulations for oral drug delivery were explored to verify ampicillin controlled release from HPMC: tablets and gelatine capsules of coprecipitated microparticles. Tablets released 97% of AMP in more than 72 h, allowing a slower drug release than capsules, that released 100% of AMP in 8 h. Drug release mechanisms characteristic of swelling-controlled systems were observed, with ampicillin release rate dominated by the erosion of HPMC matrix. (c) 2008 Elsevier B.V. All rights reserved.