Non-Dispersive Reaction and Separation Processes for Pharmaceutical Synthesis

药物合成的非分散反应和分离过程

• 批准号: 8833554
• 负责人: Tania Betancourt
• 金额: $ 15万
• 依托单位: CHEMTOR, LP
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8833554
• 关键词: Adopted; Alkylation; Amines; Area; Businesses; Chemical Engineering; Chemistry; Complex; Computer software; Data; Development; Disadvantaged; Drug Industry; Due Process; Engineering; Equipment; Experimental Designs; Fiber; High Pressure Liquid Chromatography; Indoles; Industry; Interphase; Journals; Laboratories; Letters; Marketing; Methods; Metoprolol; Modeling; Monitor; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plants; Principal Investigator; Procedures; Process; Prodrugs; Production; Pyrroles; Reaction; Reagent; Recovery; Reproducibility; S Phase; Small Business Technology Transfer Research; Statistical Models; Stream; Surface; System; Techniques; Technology; Technology Transfer; Texas; Time; Translating; Universities; Work; base; commercialization; cost; design; design and construction; interfacial; manufacturing process; prevent; process optimization; prospective; prototype; public health relevance; research and development; research study; scale up

DESCRIPTION (provided by applicant): A number of pharmaceutical reactions and wash processes involve interaction between immiscible phases within reactors or extraction equipment. Multi-phase synthesis processes have been traditionally been carried out through dispersion of one of the phases into the other in the form of droplets. Such arrangement increases the surface area of interaction, thereby increasing the rate of mass transfer between the phases. Dispersions are undesirable in large- scale processes due to the need for high energy mixing, the presence of dead volume leading to unreacted reagents, and the need for time and energy-intensive separation processes to coalesce the phases for further recovery or treatment. More recently, engineered microreactors have been introduced as alternatives that can provide high surface-to-volume ratios for interphase interaction. Unfortunately, microreactors are best suited for laboratory scale processes as they require highly complex designs to maintain design parameters upon scale up. This high complexity can translate into downtime and less-than-optimal results in industrial scale pharmaceutical processes. This Phase I Small Business Technology Transfer (STTR) project focuses on the development of non-dispersive reaction and separation platform processes for pharmaceutical syntheses that will provide significant benefits to the industry. The main objectives of the Phase I project will e to: (1) build a Phase I reactor system prototype, (2) develop methods for demonstration of pharmaceutical syntheses, (3) optimize process parameters to achieve high throughput, conversion, and product recovery, and (4) prepare for Phase II by identifying parameters where optimization will be required, performing thorough market analysis, and establishing partnership with commercial collaborators. To achieve these aims, the team will utilize the proposed fiber reactor platform system for the synthesis of pharmaceutical reagents through N-alkylations, which are representative of many reactions utilized in pharmaceutical processes. Product streams will be characterized for the identity and purity of the products with standard analytical equipment. Completion of Phase I aims will demonstrate the versatility and benefits of the proposed nondispersive reactor platform in terms of throughput, conversion, and process control compared to batch processes, while pointing out the main aspects of process optimization required for successful commercialization. Successful completion of this project would result in an inexpensive, robust, easily-scalable platform technology that could be easily adopted by the pharmaceutical industry for the synthesis of fine reagents through multi-phase processes.

描述（由申请人提供）：许多药物反应和洗涤过程涉及反应器或萃取设备内不混溶相之间的相互作用。多相合成过程传统上是通过将一相以液滴形式分散到另一相中来进行的。这种布置增加了相互作用的表面积，从而增加了相之间的传质速率。由于需要高能量混合、存在导致未反应试剂的死体积以及需要时间和能量密集型分离过程来聚结各相以进行进一步回收或处理，因此在大规模过程中分散是不期望的。最近，工程微反应器作为替代品被引入，可以为相间相互作用提供高表面体积比。不幸的是，微反应器最适合实验室规模的工艺，因为它们需要高度复杂的设计来在放大时维持设计参数。这种高度复杂性可能会导致工业规模制药过程中的停机时间和不太理想的结果。第一阶段小型企业技术转让 (STTR) 项目重点开发用于药物合成的非分散反应和分离平台工艺，这将为行业带来显着效益。第一阶段项目的主要目标将是：(1) 建造第一阶段反应器系统原型，(2) 开发药物合成示范方法，(3) 优化工艺参数以实现高通量、转化率和产品回收率(4) 通过确定需要优化的参数、进行彻底的市场分析以及与商业合作者建立伙伴关系来为第二阶段做好准备。为了实现这些目标，该团队将利用所提出的纤维反应器平台系统通过 N-烷基化合成药物试剂，这代表了制药过程中使用的许多反应。将使用标准分析设备对产品流的特性和纯度进行表征。第一阶段目标的完成将证明所提出的非分散反应器平台在吞吐量、转化率和工艺控制方面与间歇工艺相比的多功能性和优势，同时指出成功商业化所需的工艺优化的主要方面。该项目的成功完成将产生一种廉价、强大、易于扩展的平台技术，制药行业可以轻松采用该技术，通过多相工艺合成精细试剂。