PROCESS DEVELOPMENT FOR THE SYNTHESES OF ESSENTIAL MEDICINES IN CONTINUOUS FLOW
A significant number of resources are allocated to maintaining the resiliency of pharmaceutical supply chain as failure to do so thoroughly can result in drug shortages of essential medicines. Recently, the effects of COVID-19 exacerbated flaws in the current system causing the pharmaceutical industry and government organizations and to reassess relief strategies that could also strengthen the supply chain. Flow chemistry has become an attractive and prominent platform enabling continuous manufacturing (CM) technologies to synthesize active pharmaceutical ingredients (API) quickly according to demand. Compared to traditional batch chemistry, flow chemistry has demonstrated to be more robust in terms of throughput, scalability, and hazard reduction while maintaining a high degree of control and product quality. This work demonstrates these capabilities in reaction optimization and discovery with the overarching goal of domesticating CM to make essential medicines more affordable. A two-step process for the synthesis in diazepam was developed using a Chemtrix Labtrix S1 and Start microfluidic systems where purities as high as 98% were achieved. The system was successfully scaled up to a larger system that was able to produce 96% pure diazepam at a 91% yield.