(121f) Liquid-Liquid Extractions in API Manufacturing Processes: Is Continuous the Way to Go?

Extraction and separation operations are present in most API processes, in different stages, and with different purposes. Both unit operations are traditionally carried out under batch mode in multi-purpose reactors and consist in two/three sequential steps of mixing immiscible liquids with different densities and then separate them by gravity, which results in a time-consuming stage. Moreover, sometimes emulsions are obtained leading to difficulties in phase separation with impact in cycle time, yield and, potentially, product quality. Another bottleneck from these operations is related to the reactor occupancy at this stage, considering that usually one phase is carried forward and the other is discarded, which results in a limitation of batch size and production capacity.

To tackle all these operation deficiencies, continuous manufacturing is an attractive approach. The main drivers associated when going from batch to continuous highlight the opportunity to improve reproducibility, capacity, faster development, among others. For extraction and separation processes, several alternatives are available in the market with different characteristics and advantages.

In this work, we demonstrate our approach in selecting technologies for continuous process of extraction and separation, and case studies with different purposes such as pH adjustments, product/API transfer between phases and washings. The examples will show characteristics of the selected technologies (membrane based separator and centrifugal extractor) and types of liquid-liquid extraction and separation process evaluated along with the impacts resulting from going from batch to continuous manufacturing.