(191b) Characterizing Continuous Extraction and Separation Platforms for API Manufacturing: Enabling Cycle Time Reduction and Enhanced Product Stability

Operating pharmaceutical processes continuously affords several benefits over batch, including cycle-time reduction, handling of unstable intermediates and products, enhanced analytical data, and ability to operate at increased temperature and pressure conditions not safely feasible in large batch operations. An end-to-end process, including reaction and work-up steps, is desirable to capitalize on all of these advantages. Liquid-liquid extraction and separation are critical purification operations that have been demonstrated here, continuously across several platforms with model solvent systems in addition to a real pharmaceutical process stream.

Several flow extraction and separation technologies offered by Zaiput and Rousselet Robatel will be described. The SEP-10 platform by Zaiput Technologies continuously separates streams based on membrane wettability and the interfacial tension between solvents. The single stage unit and the MS-10, which was operated with up to five stages in a counter-current extraction configuration were characterized. Robatel’s platforms directly couple extraction and separation; the separation is density dependent and accelerated by the centrifugal force within the rotating bowl. These centrifugal separators have been operated as a single stage and with up to four stages in series. Preliminary characterization with solvents demonstrated close alignment between the extraction efficiency of these continuous operations with theoretical thermodynamic values for all configurations. With a real pharmaceutical process stream, API retention and impurity removal was demonstrated to be in-line with batch and thermodynamic results with the added benefit of directly telescoping with preceding continuous reaction steps to afford greater product solution stability.