Solvent-Free, Continuous Synthesis of Hydrazone-Based Active Pharmaceutical Ingredients by Twin-Screw Extrusion

Twin-screw extrusion (TSE) was used to synthesize hydantoin-based active pharmaceutical ingredients (APIs) such as nitrofurantoin and dantrolene, employing minimal or no solvent. Postsynthetic workup was not required. This work demonstrates that solvent-free synthesis can be conducted in a continuous manner for pharmaceutical products.