Flow photochemistry fundamentals, applications, and perspectives in the pharmaceutical industry

Abstract: Photochemistry continues to increase in popularity in the design of small molecules. Visible-light photochemistry typically offers mild reaction conditions and high selectivity, both hallmarks of greenness and sustainability, making it an attractive option for the commercial manufacturing of active pharmaceutical ingredients (APIs). Even with the increasing number of photochemical transformations and methodologies available in the literature, scaling up photochemical reactions for commercial manufacturing remains a significant challenge in the pharmaceutical industry. Proper scale-up of photochemical reactions requires understanding of the reaction kinetics, the rate of photon absorption in the system, thermodynamics, and other transport phenomena. Per the famous Beer-Lambert law, the attenuation of light in chemically reacting systems imposes scale-up challenges for all photochemical reactions. Myriads of reactor-light source configurations and permutations are possible from lab to commercial scales, making replication of literature and bench protocols across scales challenging without the proper understanding of the key scale-up factors and considerations. This talk will discuss fundamental aspects of photochemical reaction engineering, applications to flow photochemistry using laser-driven CSTRs as a platform, and general perspectives on scaling up photochemical reactions in the pharmaceutical industry. Flow systems offer high throughput in a small footprint, providing an effective, scalable solution for the attenuation of light in photochemical reactions. This talk will highlight how application of fundamental principles of photochemical reaction engineering can achieve kilogram-scale throughput in laboratory-scale equipment using a laser as a high intensity light source. This methodology easily extends to scalable reactor design for commercial manufacturing. The talk will conclude with perspectives on photochemical reaction engineering in the pharmaceutical industry, including how to approach process modeling, suggested best practices, and other considerations.