Process Development and Modeling of a Continuous Biphasic Liquid-Liquid System

Many pharmaceutical companies are beginning to adapt from batch to continuous manufacturing due to the numerous potential advantages it offers such as reduced waste, improved heat and mass transfer, and lower operational and capital costs. While continuous manufacturing has been widely used in the chemical industry, batch processes still dominate the pharmaceutical industry, presenting a series of regulatory, analytical, and process development challenges for adoption. Pharmaceuticals, as relatively low volume products, have generated a novel market for continuous microreactors, which still require sufficient understanding of scale-dependent parameters that can be illuminated via reactor characterization. Equipment characterization provides the ability to create enhanced process models, which are critical in process understanding and control to ensure an efficient, high quality product.

This particular study investigates a basic hydrolysis reaction in a continuous biphasic liquid-liquid system. In this system, the reaction kinetics are faster than the mass transfer rate, requiring an understanding of liquid-liquid mass transfer kinetics as a function of process variables. The reaction is performed in a Corning Low Flow (LF) reactor with extensive mixing and heat transfer performance as well as theoretical scale-up factors to the Corning G1 for pilot plant production. The objective of this project was to develop a transient model for the LF unit of the mass transfer coefficient (kLa) as a function of temperature, flow rate, and residence time for improved process control and understanding.