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: 10545666
• 负责人: Andrea Adamo
• 金额: $ 108.03万
• 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 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10545666
• 关键词: Acetone; Address; Adopted; Amendment; Chemicals; Development; Devices; Experimental Designs; Film; Goals; Grant; Hybrids; Hydrophobicity; Investments; Lasers; Lead; Liquid substance; Location; Logistics; Manufacturer Name; Membrane; Methodology; Methods; Modernization; Modification; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plants; Play; Process; Production; Productivity; Property; Reaction; Resistance; Role; Sales; Small Business Innovation Research Grant; Solid; Surface; System; Techniques; Technology; Tensile Strength; Testing; Time; Toluene; United States; Water; Work; base; chemical synthesis; commercialization; cost; design; design-build-test; drug production; ethyl acetate; experimental study; flexibility; hydrophilicity; improved; innovation; manufacturing facility; manufacturing process; novel; novel strategies; operation; portability; pressure; prototype; 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 have addressed the key technological innovations needed to enable the proposed innovation. In Phase II we are planning to demonstrated scalability of the Phase I findings; develop a suitable packaging approach for low cost, chemically resistant separation modules; build and test in a plant facility a complete, user-friendly high capacity continuous LLE system compatible with large-scale batch-based pharmaceutical production. 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， 大型反应堆在连续流中的合成（在合成期间化学品连续流动） 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 讨论了实现拟议创新所需的关键技术创新。在 第二阶段，我们计划展示第一阶段调查结果的可扩展性;制定一个合适的 低成本、耐化学腐蚀的分离模块的封装方法; 一个完整的，用户友好的高容量连续液液平衡系统， 大规模批量制药生产。 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。