Abstract
Progress in continuous flow chemistry over the past two decades has facilitated significant developments in the flow synthesis of a wide variety of Active Pharmaceutical Ingredients (APIs), the foundation of Continuous Pharmaceutical Manufacturing (CPM), which has gained interest for its potential to reduce material usage, energy and costs and the ability to access novel processing windows that would be otherwise hazardous if operated via traditional batch techniques. Design space investigation of manufacturing processes is a useful task in elucidating attainable regions of process performance and product quality attributes that can allow insight into process design and optimization prior to costly experimental campaigns and pilot plant studies. This study discusses recent demonstrations from the literature on design space investigation and visualization for continuous API production and highlights attainable regions of recoveries, material efficiencies, flowsheet complexity and cost components for upstream (reaction + separation) via modeling, simulation and nonlinear optimization, providing insight into optimal CPM operation.
Highlights
Increasing pharmaceutical Research and Development (R&D) expenditures necessitate the need for leaner manufacturing with reduced costs
The demonstration of continuous flow chemistry of an APIEiRsRtEhVeIEfWoundation of any Continuous Pharmaceutical Manufacturing (CPM) process; subsequent5pofu2r4ification + separation and Drug Product (DP) formulation unit operations are often challenging and exp2e.5n.1s.iCveonptirnoucoeusssFelsotwhaSyt nmthuessitsbe considered in the comparative evaluation of different designs
Design space investigation of CPM is a useful task in elucidating the attainable regions of operation and process efficiency and attainable product quality
Summary
Increasing pharmaceutical Research and Development (R&D) expenditures necessitate the need for leaner manufacturing with reduced costs. The chemistry, chemical engineering and process systems engineering communities have approached both unit operation and plantwide Continuous Pharmaceutical Manufacturing (CPM) from both experimental (laboratory and pilot plants) and theoretical (mathematical modeling, simulation and optimization) perspectives to elucidate promising designs for continuous API production [3,4]. Our group has conducted many studies in technoeconomic modeling, simulation and optimization of CPM for a variety of APIs, including both upstream plants (flow synthesis + purification/separation) and isolated separation trains (e.g., crystallization cascades). An understanding of the attainable performances within design spaces for different APIs that have been realized as amenable to CPM (from studies in the literature) can be useful in elucidating technoeconomic viability vs existing processes. We discuss the need for design space investigation and visualization for CPM design, followed by a review of some pertinent literature, including API flow synthesis, purification/separation and downstream unit operations. A critical discussion of these cases is provided with an outlook to the future of this vibrant research field
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
