(727e) Application of Supercritical Fluid Technology in Drug Linker Process Development

Crystallization is the most important purification and isolation process in pharmaceutical industry. However, many drug linkers, the principal component of antibody-drug conjugates (ADC), and their synthetic intermediates are relatively complex molecules which are very difficult to produce in a crystalline state, requiring multi-step preparative chromatography, solvent-exchange and lyophilization. In the present work, we explore an alternative process utilizing supercritical carbon dioxide (SC CO₂) for precipitation of amorphous and semi-crystalline materials, combined with simultaneous filtration, and drying as a single process step. The effects of pressure, temperature, and solvent composition on selective extraction of impurities, solid structure modification and particle size are discussed. It is shown that the SC technique, although structure-specific, can be tailored for screening at small-scale, high-yield isolation / purification of materials under development, also offering a good potential for kilo-lab scale production.