Bulk Dynamic Spray Freeze-Drying Part 2: Model-Based Parametric Study for Spray-Freezing Process Characterization.
Bulk Dynamic Spray Freeze-Drying Part 2: Model-Based Parametric Study for Spray-Freezing Process Characterization.
复制标题
整体动态喷雾冷冻干燥第 2 部分：喷雾冷冻过程表征的基于模型的参数研究。
DOI：
10.1016/j.xphs.2019.01.011
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Alina A. Alexeenko
中科院分区：
文献类型：
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作者：
I. Sebastião;Bakul S Bhatnagar;Serguei Tchessalov;S. Ohtake;M. Plitzko;B. Luy;Alina A. Alexeenko
喷雾冷冻干燥是一种不断发展的技术，它结合了喷雾干燥和常规冻干技术的优点，以生产自由流动的粉末状原料药和制剂。与亚毫米喷雾冷冻颗粒相关的高表面积与体积比有助于缩短干燥和重构时间。冷冻颗粒的形成是这种脱水技术中最关键的部分，因为它决定了最终产品的特性。基于先前提出和验证的模型，当前的目标是了解喷雾冷冻过程中各种可控参数的作用。更具体地说，给定一组喷雾条件，该模型用于预测将液滴冷却和冷冻到低于防止聚结和产物附聚的温度所需的最小距离。进行了参数研究，以映射考虑中的实际喷雾冷冻柱装置的操作极限条件。对于感兴趣的喷雾冷冻干燥条件，模型模拟表明，对流有助于至少80%的总液滴传热，因此，冷冻柱气体温度和液滴直径是影响冷冻距离的最重要的工艺参数。
Spray freeze-drying is an evolving technology that combines the benefits of spray-drying and conventional lyophilization techniques to produce drug substance and drug product as free-flowing powders. The high surface-to-volume ratio associated to the submillimeter spray-frozen particles contributes to shorter drying and reconstitution times. The formation of frozen particles is the most critical part of this dehydration technique because it defines the properties of final product. Based on a previously proposed and validated model, the current goal is to understand the role of various controllable parameters in the spray-freezing process. More specifically, given a set of spraying conditions, the model is used to predict the minimum distance required to cool and freeze the droplets below a temperature that prevents coalescence and product agglomeration. A parametric study is carried out to map the operational limit conditions of the actual spray-freezing column apparatus under consideration. For the spray freeze-drying conditions of interest, model simulations indicate that convection contributes to at least 80% of the total droplet heat transfer and, consequently, that freezing column gas temperature and droplet diameter are the most important process parameters affecting the freezing distance.