Application of multiobjective optimization in the deisgn of simulated moving bed systems for chiral drug separation

多目标优化在手性药物分离模拟移动床系统设计中的应用

• 批准号: 326840-2006
• 负责人: Ray, AjayKumar
• 金额: $ 1.78万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=397437
• 关键词: Application; multiobjective; optimization; deisgn; simulated

The sale of chiral drugs is close to one third of all drug sales worldwide. Ordinary chemical production methods for chiral drugs produce a racemic mixture containing enantiomers having identical chemical compositions but different structrtal orientation in space. It is quite common to find that one isomeric form of a chiral drug has a therapeutic effect on the human body while its enantiomer is harmful. When one isomer is 'good' and the other 'bad', there is obvious benefit from separating the two enantiomers to enhance its safety and tolerability. The Simulated Moving Bed (SMB) system is a viable technology for obtaining pure single enantiomers. Lately, there has been increased interest in the pharmaceutical industry for using SMB technology for enantio-separations due to recent developments in chiral stationary phases and nonlinear chromatographic theory, as well as stringent drug administration policy. Enhanced productivity satisfying stringent product qualities and significant cost savings are possible if optimal design of the SMB is made. In this project, we propose to study in detail the separation and purification of chiral drugs, particularly, for racemate mixtures containing more than two enantiomers. Our main emphasis is in new design and development, and application of multi-objective optimization and advanced real-time control to SMB systems. Detailed simulation models would be developed, which will subsequently be verified experimentally. Thereafter, optimal operating conditions will be computed using multiple objectives and constraints. An adaptation of the state-of-the-art optimization technique, genetic algorithm, will be used. Finally, optimal operating performance would be validated experimentally. These studies would help optimize several objectives while simultaneously satisfying numerous real-life constraints encountered in industry.

手性药物的销售接近全球所有药物销售的三分之一。手性药物的普通化学生产方法产生了一种外围混合物，其中含有具有相同化学成分但空间中不同构成方向的映异构体。很常见的是，手性药物的一种异构体形式对人体具有治疗作用，而其对映异构体有害。当一个异构体是“好”而另一个“坏”时，将两个对映异构体分开以增强其安全性和耐受性会有明显的好处。模拟的移动床（SMB）系统是一种可行的技术，用于获得纯单一对映异构体。最近，由于手性固定阶段和非线性色谱理论以及严格的药物管理政策，对制药行业对使用SMB技术进行对映射分离的兴趣增加了。如果制定了最佳的SMB设计，则可以提高生产力满足严格的产品质量和大量成本。在这个项目中，我们建议详细研究手性药物的分离和纯化，特别是对于含有两个以上对映异构体的种族混合物。我们的主要重点是新的设计和开发，以及多目标优化和高级实时控制在SMB系统中的应用。将开发详细的仿真模型，随后将通过实验验证。此后，将使用多个目标和约束来计算最佳操作条件。将使用最先进的优化技术遗传算法的适应。最后，最佳的运营性能将通过实验验证。这些研究将有助于优化几个目标，同时满足行业中遇到的许多现实生活限制。