The application of three supercritical processes to the micronization of gastroresistant insulin formulations is presented. As pharmaceutical applications of the supercritical anti-solvent micronization processes are becoming established at the bench scale, it is timely that they are compared in terms of product characteristics and scalability aspects. The formulation of insulin with the gastroresistant coating hydroxypropyl methyl cellulose phthalate was conducted by the Gas Anti-Solvent (GAS), the Aerosol Solvent Extraction System (ASES) and the Atomized Rapid Injection for Solvent Extraction (ARISE) processes and results have been compared in terms of insulin content of the microparticles, product morphology and recovery. The insulin content in products was in the range of 9-47%. The particles produced by the GAS process were flake-like in the 1-2 mu m range with bi-modal distribution, while particles produced by the ASES and ARISE processes were spherical in the 100-300 nm particle size range with unimodal size distribution. Compared to GAS and ASES, the ARISE process produced the highest recoveries and insulin loadings: 77% and 47%, respectively. Particle characteristics, process recoveries and operational aspects indicate that ARISE should be the process of choice for scale-up. (C) 2015 Elsevier B.V. All rights reserved.