Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands.
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands.
Eur J Pharm Sci. 2019 Feb 1;128:152-157. doi: 10.1016/j.ejps.2018.11.027. Epub 2018 Dec 3.
The aim of this study was to identify critical steps to protein stability during spray drying using two different nozzle types: a vibrating mesh nozzle and a standard two-fluid nozzle in a Büchi B-90 spray dryer. l-Lactic dehydrogenase was used as a model protein as it is a heat and shear stress sensitive protein. Trehalose was used as excipient because of its excellent stabilizing capacities. The entire spray drying process was split up into smaller steps and after each step the enzymatic activity of the protein was measured. With the vibrating mesh nozzle in total 78% of activity was lost. About 68% was due to atomizing and heating and 10% was caused by dehydration and circulation of the liquid. With the two-fluid nozzle the total activity loss was only 23%, to which atomization, dehydration, and circulation contributed almost equally. Heating was not an issue, as the two-fluid nozzle could be cooled with water. In conclusion, the type and the configuration of the nozzle used for spray drying are important determinants for maintaining protein stability, as atomizing, heating, ultra-sonication, and recirculation of the feed solution negatively influence it. The possibility to cool the two-fluid nozzle offers an important advantage to the vibrating mesh nozzle in the spray drying process of proteins. In this study, we show that, next to the optimization of the formulation, optimization of the spray drying process should be taken into account to maintain protein stability.
本研究的目的是确定使用两种不同喷嘴类型（振动筛式喷嘴和标准双流喷嘴）在 Büchi B-90 喷雾干燥器中喷雾干燥过程中蛋白质稳定性的关键步骤。选择 l-乳酸脱氢酶作为模型蛋白，因为它是一种对热和剪切力敏感的蛋白质。使用海藻糖作为赋形剂，因为它具有出色的稳定能力。整个喷雾干燥过程被分解为更小的步骤，并且在每个步骤之后测量蛋白质的酶活性。使用振动筛式喷嘴，总活性损失了 78%。约 68%是由于雾化和加热引起的，10%是由于脱水和液体循环引起的。使用双流喷嘴，总活性损失仅为 23%，其中雾化、脱水和循环几乎同等贡献。由于双流喷嘴可以用水冷却，因此加热不是问题。总之，用于喷雾干燥的喷嘴的类型和结构是保持蛋白质稳定性的重要决定因素，因为雾化、加热、超声和进料溶液的再循环会对其产生负面影响。双流喷嘴能够冷却提供了在蛋白质喷雾干燥过程中的一个重要优势。在这项研究中，我们表明，除了优化配方外，还应考虑优化喷雾干燥工艺以保持蛋白质稳定性。
