Non-Dispersive Reaction and Separation Processes for Pharmaceutical Synthesis

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提取设备内不相容相之间的相互作用。传统上，多相合成过程是通过将一相以液滴的形式分散到另一相中来进行的。这种排列增加了相互作用的表面积，从而增加了相之间的传质速率。在大规模过程中，分散是不可取的，因为需要高能量混合，存在死体积导致未反应的试剂，以及需要时间和能量密集型的分离过程来结合相以进行进一步的回收或处理。最近，工程化的微反应器被引入作为替代方案，它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过程，因为它们需要高度复杂的设计来在放大后保持设计参数。在工业规模的制药过程中，这种高度的复杂性可能会导致停机时间和不太理想的结果。这一第一阶段小型企业技术转让(STTR)项目专注于为药物合成开发非分散反应和分离平台工艺，这将为该行业带来重大好处。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，以及(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合作伙伴关系，为第二阶段做准备。为了实现这些目标，该团队将利用拟议的纤维反应器平台系统通过N-烷基化反应合成药物试剂，N-烷基化反应是制药过程中使用的许多反应的代表。产品流将用标准分析设备表征产品的特性和纯度。第一阶段目标的完成将展示与间歇工艺相比，拟议的非分散反应器平台在生产能力、转化率和工艺控制方面的多功能性和优势，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带来一种廉价、坚固、易于扩展的平台技术，该技术可以很容易地被制药行业采用，通过多阶段过程合成精细试剂。

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.