During a protein spray drying process, thermal and mechanical stresses are exerted on the proteins leading to degradation. We hypothesize that in situ measurements of the droplet size, temperature distribution inside droplets and UV fluorescence will prov

在蛋白质喷雾干燥过程中，热应力和机械应力作用于蛋白质，导致蛋白质降解。

基本信息

批准号：
315006086
负责人：
Professor Dr.-Ing. Lutz Mädler
金额：
--
依托单位：
Fachgebiet Mechanische Verfahrenstechnik
依托单位国家：
德国
项目类别：
Priority Programmes
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/315006086?language=en
关键词：
During protein spray drying process

项目摘要

Protein processing and formulating often involves the removal of excess water. Spray drying is one of the most widely used unit operations for the production of stable protein containing powders. In spray drying a stock solution is atomized while subsequent evaporation increases the protein concentration within the evaporating droplets. During this drying process, thermal and mechanical stresses are exerted on the proteins that can result into degradation. Depending on the polar groups of the proteins they will accumulate at the air-water interface, forming a surface layer of proteins oriented in such a way that their hydrophilic parts are exposed to water which can cause unfolding.A fundamental understanding of the mechanisms of protein degradation is important for designing a spray drying process. The kinetics and interactions of such thermal and mechanical stresses on proteins are, however, not well understood at the single droplet level. There is no study on the time resolved kinetics of the denaturation processes at the droplet level.Experiments with single droplets are a common technique to investigate the basics of spray drying. Single droplets experiments will be conducted using a piezoelectric droplet generator in a drying chamber. The droplet size will be monitored with a camera and Mie scattering imaging. This method also gives information on the formation of aggregates and precipitation within a droplet. Temperature and protein concentration profiles will be measured with the Rainbow technique. We will use fluorescence spectroscopy with specific fluoresce dyes to monitor the unfolding and denaturation of the proteins.Our objective is a relationship between spray drying process parameters such as, droplet size, protein concentration and protein functional groups, solution additives as well as gas composition and temperature and the degradation kinetics. We hypothesize that time resolved, in situ measurements of the droplet size, temperature distribution inside droplets and protein UV fluorescence will provide degradation kinetics.

蛋白质加工和配制通常涉及去除多余的水。喷雾干燥是生产稳定的含蛋白质粉末的最广泛使用的单元操作之一。在喷雾干燥中，原液被雾化，而随后的蒸发增加了蒸发液滴内的蛋白质浓度。在干燥过程中，蛋白质会受到热应力和机械应力，从而导致蛋白质降解。根据蛋白质的极性基团，它们会在空气-水界面积聚，形成蛋白质表面层，其亲水部分暴露在水中，从而导致展开。对蛋白质机制的基本了解降解对于喷雾干燥工艺的设计非常重要。然而，这种热应力和机械应力对蛋白质的动力学和相互作用在单液滴水平上还没有得到很好的理解。目前还没有关于液滴水平变性过程的时间分辨动力学的研究。单液滴实验是研究喷雾干燥基础知识的常用技术。单液滴实验将在干燥室中使用压电液滴发生器进行。将使用相机和米氏散射成像来监测液滴尺寸。该方法还提供了有关液滴内聚集体形成和沉淀的信息。将使用 Rainbow 技术测量温度和蛋白质浓度分布。我们将使用具有特定荧光染料的荧光光谱来监测蛋白质的展开和变性。我们的目标是喷雾干燥工艺参数之间的关系，例如液滴大小、蛋白质浓度和蛋白质官能团、溶液添加剂以及气体成分和温度和降解动力学。我们假设时间分辨的液滴尺寸、液滴内的温度分布和蛋白质紫外荧光的原位测量将提供降解动力学。