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.

项目摘要/摘要 国内药品制造业正在努力满足需求。因此是 必须开发工具以快速提高现有生产工厂的生产率。 目前，药品的制造几乎完全依赖于批处理化学物质 合成。在这种方法中，化学合成发生在内部的几个单独步骤中 大反应堆。连续流中的合成（化学物质在过程中连续流动 反应过程）正在成为更有效的替代方案。但是，连续合成 由于几个实际原因，流量并未被广泛采用，包括需要 投资大修现有生产工厂。 液 - 液体提取（LLE）代表药物中最常见的后反应步骤 合成。重要的是，虽然当前在批处理中用于LLE的技术 合成是一种大幅降低过程效率的瓶颈，在 连续流程效率高。目前无法使用LLE的现有技术 在基于批处理的制造厂，因为它们的最大流量太低而无法满足 对基于批处理的生产工厂的需求。 在这里，我们建议开发一个新颖，高容量的系统，以在连续流中实施LLE 在基于批处理的药物合成的背景下。我们设想一个插件，便携式， 高流量，可以在没有的药品生产工厂中部署的自我调整设备 需要大修生产过程。为了构建该系统，在此SBIR的第一阶段中，我们 将解决建立自动，高能力所需的关键技术创新 连续LLE系统与大规模批处理的药物生产兼容。 也就是说，我们将：1）开发一个能够处理高的流动流动液萃取系统 （动荡的）流速和2）我们将开发一个能够自动托管压力控制系统 支持使用最小的外部控制设备的操作。在第二阶段 SBIR，我们将利用这些技术创新来创建一个用户友好的 产品准备在现有药品生产工厂内部署。 如果成功，该项目将产生能够立即提高生产率的工具 现有的制药植物从2到5倍。该产品将重新定义 美国及其他地区的药物生产。