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

项目摘要/摘要 国内制药业正在艰难地满足需求。因此，它是 必须开发工具，迅速提高现有生产工厂的生产率。 药品的生产目前几乎完全依赖于批量生产的化学品。 综合。在这种方法中，化学合成在以下几个单独的步骤中进行 大型反应堆。连续流动中的合成(化学品在连续流动过程中 反应过程)正在成为一种更有效的替代方法。然而，连续合成 由于几个实际原因，Flow没有被广泛采用，包括需要主要的 对现有生产工厂进行全面改造的投资。 液-液萃取(LLE)是制药中最常见的反应后步骤 综合。重要是，虽然当前在批处理上下文中用于LLE的技术 合成是显著降低工艺效率的瓶颈，LLE提取在 连续流动是非常高效的。现有的LLE In Flow技术目前不能使用 因为它们的最大流量太低，不能满足 以批量为基础的生产工厂的需求。 在这里，我们建议开发一种新的、大容量的系统来实现连续流中的液液平衡。 在基于批次的药物合成的背景下。我们设想一种即插即用、便携、 高流量、自调整设备可在现有制药厂部署，而无需 需要彻底改革生产流程。为了建立这个系统，在这个SBIR的第一阶段，我们 将解决建设自立、高能力所需的关键技术创新 与大规模批量制药生产兼容的连续液液平衡系统。 也就是说，我们将：1)开发一种能够处理高密度的连续流液-液萃取系统 (湍流)流速和2)我们将开发一种自调节压力控制系统，能够 以最小的外部控制支持此类设备的操作。在这个项目的第二阶段 SBIR，我们将利用这些技术创新创造一个人性化的 产品已准备好在现有的药品生产工厂内部署。 如果成功，该项目将产生一种工具，能够立即提高 现有制药厂从2倍增加到5倍。这款产品将重新定义 在美国和其他地方的药品生产。

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.