High-Throughput Extractions: A New Paradigm for Workup Optimization in Pharmaceutical Process Development

Abstract

In the pharmaceutical industry, high throughput (HT) technology is well developed and routinely utilized in chemical process development for reaction optimization and isolations via crystallization. However, fewer HT technologies have been employed in the development of workup procedures, bridging optimized reaction and isolations. Frequently, extensive workups involving numerous unit operations are required to remove reaction stream components, such as impurities, solvent, and catalyst, prior to isolation. Herein, we describe a systematic yet flexible approach using designed experimentation, laboratory automation, and parallel experimentation to quickly and efficiently optimize unit operations that are required post reaction to remove reaction stream components (e.g., impurities, metal catalysts, solvent). This novel high throughput extraction (HTEx) platform has shown potential to broadly impact development by faster and more robustly improving process greenness, process mass intensity (PMI), cycle time...