(58a) Developing a Workflow for Continuous Centrifugal Extraction

Liquid-liquid extraction is ubiquitous throughout API process development as a method to purify reaction mixtures. On paper, extraction is a straightforward, effective unit operation in which two immiscible liquids are mixed to extract specific components from one liquid phase to the other. In practice, extractions can pose problems as they are scaled up from development work to manufacturing scales. Traditionally, extraction in the pharmaceutical industry is performed in batch mode in stirred tanks, which can lead to long settling times and inefficient use of solvent. Furthermore, the presence of surfactants or the over-agitation of the two liquids may lead to emulsification, which significantly complicates the gravity-driven separation of the two liquids. Prolonged settling times increase the cycle time of the process, reducing overall throughput and may risk degrading reactive intermediates as the liquids remain in contact while settling.

Continuous extraction offers attractive, practical solutions to conventional batch extraction. First, continuous flow devices have smaller footprints compared to batch devices. Additionally, there are many types of flow contacting devices, such as mixer-settlers, packed or agitated columns, and membranes, among others, allowing flexibility for the contacting device to match the properties and needs of the two liquids in the process. One such continuous flow contacting device is a centrifugal extractor. These devices provide excellent mixing for the two liquids as they flow into the device while efficiently separating the two liquids via centrifugal force as they flow out of the device. Centrifugal extractors offer mixing and separation in the same unit to minimize the footprint, can separate liquids with small density differences, can tolerate liquids that tend to emulsify, and provide short contacting times for fast extractions or unstable intermediates. These advantages of centrifugal extractors make them attractive as options for continuous flow in the pharmaceutical industry.

This presentation describes the development work of a model system for continuous centrifugal extraction. We will describe the key features of the process, such as partition coefficient, number of equilibrium stages, and other relevant thermodynamic data. Additionally, we will highlight some of the key issues and parameters to address with scale-up and design of centrifugal extraction processes. Finally, we will detail AbbVie’s general workflow to designing and developing continuous extractions with the goal of implementing robust continuous extractions at scale.

Eric Moschetta and Benjamin Rizkin are employees of AbbVie and may own AbbVie stock. AbbVie sponsored and funded the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication.