GOALI: Modeling and Control of Fluid Dynamics and Ice Formation in Pharmaceutical Freeze-Drying

目标：药物冷冻干燥中流体动力学和冰形成的建模和控制

• 批准号: 0829047
• 负责人: Alina Alexeenko
• 金额: $ 9.32万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0829047&HistoricalAwards=false
• 关键词: GOALI; Modeling; Control; Fluid; Dynamics

0829047Alexeenko Freeze-drying is widely used in pharmaceutical manufacturing to extend the shelf life of medical drugs and to provide easy shipping and storage. The goal of freeze-drying is to remove the solvent in such a way that the sensitive molecular structure of the active substance of a drug is least disturbed, and to provide a sterile powder that is quickly and completely rehydrated upon the addition of water. This is done by fast freezing followed by sublimation. Freeze-drying is both a time- and energy-intensive manufacturing process. For example, freeze-drying of 50 milliliters of an experimental protein drug takes up to three days and more than 2,000,000 BTU of energy. Currently, the design of freeze-drying equipment, both laboratory-scale and industrial, is based largely on empirical knowledge. The PIs will apply numerical simulations of vapor and non-condensable gas transport in a freeze-dryer chamber and develop models of vapor/ice interphase transport in a condenser. These large-scale simulations will model vapor and noncondensable gas flow and ice formation in freeze-drying using computational fluid dynamics and the direct simulation Monte Carlo method. Numerical modeling will provide insight into the control of the biopharmaceutical freeze-drying process and the design of compact condensers. Experimental studies will validate the developed models by comparison position dependence of sublimation rates in a freeze-dryer chamber under controlled radiative and conductive heat transfer conditions; water vapor flow rates in the chamber-condenser connector by tunable diode laser absorption spectroscopy; ice formation rates and geometric shapes in the condenser for various condensing surface configurations and temperatures; and a wide range of chamber-to-condenser pressure ratios. The validated models and simulation approaches will form a knowledge base by which future designs of freeze-drying systems and processes will be guided in a physics-based as opposed to an empirical approach. Understanding the fluid dynamics of the water vapor and non-condensable gas as well as the dynamics of vapor/ice interface in freeze-dryers will accelerate the development of freeze-dried products and decrease drug manufacturing costs, which will have a very high societal impact.

0829047 Alexeenko冻干广泛应用于药品生产，以延长医疗药品的保质期，并提供方便的运输和储存。冷冻干燥的目的是以药物活性物质的敏感分子结构受到最小干扰的方式去除溶剂，并提供在加入水后快速且完全再水化的无菌粉末。这是通过快速冷冻然后升华来完成的。冷冻干燥是一个时间和能源密集型的制造过程。例如，冷冻干燥50毫升的实验性蛋白质药物需要长达三天的时间和超过2，000，000 BTU的能量。目前，冷冻干燥设备的设计，无论是实验室规模还是工业规模，都主要基于经验知识。PI将应用数值模拟的蒸汽和不凝性气体运输在冷冻干燥室和开发模型的蒸汽/冰相间运输在冷凝器。这些大规模模拟将使用计算流体动力学和直接模拟蒙特卡罗方法模拟冷冻干燥中的蒸汽和不凝性气体流动以及冰的形成。数值模拟将为生物制药冻干过程的控制和紧凑型冷凝器的设计提供深入的了解。实验研究将验证开发的模型比较位置依赖的升华率在冷冻干燥室在受控的辐射和传导传热条件下;水蒸汽流量在室冷凝器连接器的可调谐二极管激光吸收光谱;冰形成率和几何形状的冷凝器为各种冷凝表面配置和温度;以及宽范围的腔室-冷凝器压力比。经验证的模型和模拟方法将形成一个知识库，通过该知识库，冷冻干燥系统和工艺的未来设计将以基于物理的方法而不是经验方法为指导。了解冻干机中水蒸气和不凝性气体的流体动力学以及水蒸气/冰界面的动力学，将加速冻干产品的开发，降低药物制造成本，这将具有非常高的社会影响。