Abstract
Corticosteroid synthesis involves multiple highly exothermic reaction steps and the handling of sensitive intermediates, which pose significant process safety and operational risks. This work presents an extensive calorimetric and explosibility study of a three-step corticosteroid synthesis, aiming to optimize process safety while maintaining product quality. Differential Scanning Calorimetry (DSC), Adiabatic Calorimetry (ARC), and reaction calorimetry (RC1) were used to quantify thermal stability, reaction enthalpies, and maximum temperature of the synthesis reaction (MTSR) for each step. In parallel, dust explosibility properties of isolated intermediates were evaluated, including Minimum Ignition Energy (MIE) and Kst values. The study identified the first synthesis step as particularly critical due to its high exothermicity and the hazardous properties of the intermediate product when dried. A process redesign was proposed, eliminating the drying and isolation of the intermediate, resulting in improved safety, sustainability, and reduced operational costs. This comprehensive hazard evaluation demonstrates the importance of integrating calorimetric tools and dust explosion testing to systematically identify hazards, refine operating parameters, and design inherently safer corticosteroid production processes.
