Continuous liquid-liquid extractors for doubling of productivity and henhancement of batch based drug manufacturing

项目总结/文摘

Project Summary/Abstract Domestic pharmaceutical manufacturing is struggling to meet demands. It is therefore imperative to develop tools to rapidly increase the productivity of existing production plants. Manufacturing of pharmaceuticals currently relies almost entirely on batch-based chemical synthesis. In this approach, chemical synthesis takes place in several separate steps within large reactors. Synthesis in continuous flow (with chemicals flowing continuously during the reaction process) is emerging as a more efficient alternative. However, synthesis in continuous flow is not being widely adopted due to several practical reasons, including the need for major investments to overhaul existing production plants. Liquid-liquid extraction (LLE) represents the most frequent post-reaction step in pharmaceutical syntheses. Importantly, while technologies currently used for LLE in the context of batch synthesis are a bottleneck that dramatically reduces process efficiency, LLE extraction in continuous flow is highly efficient. Existing technologies for LLE in flow cannot currently be used in batch-based manufacturing plants because their maximum flow rate is too low to meet the demands of batch-based production plants. Here, we propose to develop a novel, high capacity system to implement LLE in continuous flow in 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 without the need to overhaul production processes. To build this system, in the Phase I of this SBIR, we will address the key technological innovations needed to build a self-standing, high capacity continuous 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 to support the operation of such a device with minimal external control. In the Phase II of this SBIR, we will take advantage of these technological innovations to create a user-friendly product ready for deployment within existing pharmaceutical production plants. If successful, this project will produce a tool able to immediately increase the productivity of existing pharmaceutical plants from 2 to 5-fold. This product will redefine the landscape of pharmaceutical production in the United States and beyond.