(732p) Facilitating Batch to Flow Process Conversion through Hands-on Training on Heat and Mass Transfer Characterization, Multiphasic Systems, and Microfluidic Equipment

The paradigm shift undertaken by the pharmaceutical and specialty chemical industries from batch to continuous-flow processing necessitates a strong understanding of the benefits of continuous operation which can be more controlled, cost-effective, and efficient than traditional batch. The work presented herein is a RAPID-funded course development project that strategically combines industry and academic expertise to provide hands-on training on key principles of batch to flow process conversion with case studies on heat transfer, mass transfer, multiphasic systems, and process automation. The training is divided into four modules, each centered around a case study relevant to the pharmaceutical industry teaching fundamentals of translating a process from batch flow and its advantages on throughput, safety, and product quality. The first module focuses on translating the exothermic decomposition of hydrogen peroxide from a batch reactor where a thermal runaway occurs, to a flow reactor that enables high temperature and pressure operation. Moreover, heat transfer coefficients and residence time distributions were obtained for batch and flow reactors to model temperature and concentration profiles and choose optimal reaction conditions for high throughput and safe operation. In flow, applying 100psi back pressure to compress the oxygen produced and increase liquid residence time led to full conversion at 70oC for a theoretical residence time of 10 minutes. The second module quantifies micro-mixing in batch and flow systems using the Villermaux-Dushman method for fast single-phase reactions in which segregation results in byproduct formation. The reactive liquid-liquid extraction of salicylic acid with integrated membrane separation is used to compare batch and flow performance and highlight the use of different micromixers in flow. The flow system with static mixer reached full conversion in a minute with a mass transfer coefficient two orders of magnitude higher than in batch where 70% was reached in an hour. The third module focuses on packed bed reactors, specifically pressure drop as a function of packing particle size and residence time distributions to quantify the degree of mixing. The curriculum developed in this work has been used to train industry professionals, professors, and graduate students in the pilot RAPID course. It was also offered to a group of high school and undergraduate women, showing the adaptability of the material to technically-diverse audiences.