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

连续液-液萃取器可提高生产率并增强批量药物生产

• 批准号: 10153085
• 负责人: Andrea Adamo
• 金额: $ 24.71万
• 依托单位: ZAIPUT FLOW TECHNOLOGIES LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10153085
• 关键词: Address; Adopted; Amendment; Chemicals; Chemistry; Development; Devices; Drops; Emulsions; Experimental Designs; Goals; Hybrids; Hydrophobicity; Investments; Lead; Liquid substance; Logistics; Manufacturer Name; Membrane; Methods; Modernization; Outcome; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plants; Play; Process; Production; Productivity; Property; Reaction; Sales; Small Business Innovation Research Grant; System; Techniques; Technology; Testing; Time; United States; Water; base; chemical synthesis; commercialization; cost; design; drug production; ethyl acetate; flexibility; hydrophilicity; improved; manufacturing process; novel; novel strategies; operation; portability; pressure; real world application; scale up; small molecule; technological innovation; tool; user-friendly

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.

项目总结/摘要 国内制药业正在努力满足需求。因此 开发工具以快速提高现有生产工厂的生产率势在必行。 制药目前几乎完全依赖于批量生产的化学品。 合成.在这种方法中，化学合成在几个单独的步骤中进行， 大型反应堆连续流合成（化学品在合成过程中连续流动） 反应过程）正在成为更有效的替代方案。然而，连续合成 由于几个实际原因，流没有被广泛采用，包括需要主要 对现有生产工厂进行大修。 液-液萃取（LLE）代表了制药工业中最常见的反应后步骤， 合成。重要的是，虽然目前用于LLE的技术在批量生产的背景下， 合成是显著降低工艺效率瓶颈， 连续流动是高效的。流中液液平衡的现有技术目前无法使用 因为它们的最大流速太低而不能满足 批量生产工厂的需求。 在这里，我们建议开发一种新颖的，高容量的系统，以实现液液平衡在连续流 在基于批量的药物合成的背景下。我们设想一个即插即用，便携式， 高流速、自调节装置，其可部署在现有制药厂中， 彻底改革生产工艺的必要性。为了建立这个系统，在SBIR的第一阶段，我们 将解决关键技术创新需要建立一个自立，高能力， 与大规模批量制药生产兼容的连续液液萃取系统。 即，我们将：1）开发能够处理高浓度的连续流液-液萃取系统。 （湍流）流速和2）我们将开发一个自调压力控制系统， 以最小的外部控制支持这种设备的操作。在第二阶段， SBIR，我们将利用这些技术创新，创造一个用户友好的 产品可在现有制药厂中部署。 如果成功，该项目将产生一个工具，能够立即提高生产力， 现有的制药厂从2到5倍。该产品将重新定义 在美国和其他地区的制药生产。