Domestic pharmaceutical manufacturing is struggling to meet demands. It is thereforeimperative to develop tools to rapidly increase the productivity of existing production plants.Manufacturing of pharmaceuticals currently relies almost entirely on batch-based chemicalsynthesis. In this approach, chemical synthesis takes place in several separate steps withinlarge reactors. Synthesis in continuous flow (with chemicals flowing continuously during thereaction process) is emerging as a more efficient alternative. However, synthesis in continuousflow is not being widely adopted due to several practical reasons, including the need for majorinvestments to overhaul existing production plants.Liquid-liquid extraction (LLE) represents the most frequent post-reaction step in pharmaceuticalsyntheses. Importantly, while technologies currently used for LLE in the context of batchsynthesis are a bottleneck that dramatically reduces process efficiency, LLE extraction incontinuous flow is highly efficient. Existing technologies for LLE in flow cannot currently be usedin batch-based manufacturing plants because their maximum flow rate is too low to meet thedemands of batch-based production plants.Here, we propose to develop a novel, high capacity system to implement LLE in continuous flowin the context of batch-based pharmaceutical synthesis. We envision a plug and play, portable,high flow rate, self-tuning device deployable in existing pharmaceutical production plants withoutthe need to overhaul production processes. To build this system, in the Phase I of this SBIR, wewill address the key technological innovations needed to build a self-standing, high capacitycontinuous LLE system compatible with large-scale batch-based pharmaceutical production.Namely, we will: 1) develop a continuous flow liquid-liquid extraction system able to handle high(turbulent) flow rates and 2) we will develop a self-tunable pressure control system able tosupport the operation of such a device with minimal external control. In the Phase II of thisSBIR, we will take advantage of these technological innovations to create a user-friendlyproduct ready for deployment within existing pharmaceutical production plants.If successful, this project will produce a tool able to immediately increase the productivity ofexisting pharmaceutical plants from 2 to 5-fold. This product will redefine the landscape ofpharmaceutical production in the United States and beyond.
Public Health Relevance Statement: Project Narrative Current pharmaceutical manufacturing is struggling to meet demands. A major bottleneck of modern pharmaceutical production is liquid-liquid extraction. Here, we propose the development of a new tool for liquid-liquid extraction that is expected to swiftly increase the productivity of existing pharmaceutical manufacturing plants 2 to 5-fold without the need for process overhaul.
Project Terms: chemical synthesis ; Chemistry ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Emulsions ; Experimental Designs ; Goals ; Hybrids ; Investments ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Methods ; Modernization ; Plants ; Play ; pressure ; Production ; Productivity ; Sales ; Technology ; Testing ; Time ; United States ; Water ; Hydrogen Oxide ; ethyl acetate ; base ; improved ; Phase ; Chemicals ; Logistics ; fluid ; liquid ; Liquid substance ; tool ; Adopted ; Reaction ; Techniques ; System ; membrane structure ; Membrane ; Hydrophobicity ; hydrophilicity ; novel ; Amendment ; technological innovation ; Devices ; Property ; portability ; drug production ; Manufacturer ; Manufacturer Name ; Drops ; Pharmaceutical Agent ; Pharmaceuticals ; Pharmacological Substance ; Pharmacologic Substance ; small molecule ; Address ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Process ; Development ; developmental ; cost ; design ; designing ; novel strategies ; new approaches ; novel approaches ; novel strategy ; Outcome ; manufacturing process ; scale up ; user-friendly ; commercialization ; real world application ; flexibility ; flexible ; operation ;
