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相之间的相互作用。多相合成工艺传统上是通过将一相以液滴的形式分散到另一相中来进行的。这样的排列增加了相互作用的表面积，从而增加了相间的传质速率。分散体在大规模工艺中是不可取的，因为需要高能量混合，存在导致未反应试剂的死体积，并且需要时间和能量密集的分离过程来合并相以进一步回收或处理。最近，工程微反应器已被引入作为替代方案，可以为间相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过程，因为它们需要高度复杂的设计来维持规模上的设计参数。在工业规模的制药过程中，这种高复杂性会导致停机时间和不太理想的结果。第一阶段小型企业技术转移（STTR）项目的重点是开发用于药物合成的非分散反应和分离平台工艺，这将为该行业带来重大利益。第一阶段项目的主要目标将是：(1)建立第一阶段反应器系统原型，(2)开发药物合成演示方法，(3)优化工艺参数以实现高通量、转化率和产品回收率，以及(4)通过确定需要优化的参数，进行彻底的市场分析，并与商业合作者建立伙伴关系，为第二阶段做准备。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，这是制药过程中使用的许多反应的代表。将用标准分析设备对产品流进行鉴定和纯度表征。完成第一阶段的目标将展示所提议的非分散反应器平台在吞吐量、转化率和过程控制方面的多功能性和优势，同时指出成功商业化所需的过程优化的主要方面。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，可以很容易地被制药行业采用，通过多相工艺合成精细试剂。