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堆或提取设备中不混溶阶段之间的相互作用。传统上，多相合成过程是通过将其中一个相分散到另一个液滴形式中进行的。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，导致未反应试剂的死亡体积以及时间和能源密集型分离过程需要与相结合以进一步恢复或治疗，因此分散在大规模过程中是不可取的。最近，已经引入了工程的微反应器作为替代方案，可以为相间相互作用提供高表面与体积比率。不幸的是，微反应器最适合实验室规模工艺，因为它们需要高度复杂的设计才能在扩大规模时保持设计参数。这种高复杂性可以转化为工业规模的药物过程中的停机时间和比最佳的结果。 I阶段的小型企业技术转移（STTR）项目着重于开发非分散性反应和分离平台流程的药物合成，这将为行业带来重大好处。第一阶段项目的主要目标将E到：（1）建立一个I期反应堆系统原型，（2）开发用于演示药品合成的方法，（（3）优化过程参数以实现高吞吐量，转换和产品恢复，以及（4）通过在需要优化参数的情况下，与彻底的市场分析一起，并为综合市场而做好一部分，并促进了综合市场，并构建了一部分分析，并促进了一部分分析。为了实现这些目标，团队将利用提出的纤维反应堆平台系统通过N-烷基化来合成药物试剂，这代表了药物过程中使用的许多反应。产品流将以标准分析设备的标识和纯度为特征。 I阶段目标的完成将证明与批处理过程相比，在吞吐量，转换和过程控制方面，提出的非分散反应堆平台的多功能性和好处，同时指出了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导致一项廉价，健壮，易于估计的平台技术，制药行业可以轻松地通过多相过程来合成精细试剂。