Development of a Novel Continuous Filtration Unit for Pharmaceutical Process Development and Manufacturing
Development of a Novel Continuous Filtration Unit for Pharmaceutical Process Development and Manufacturing
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DOI：
10.1016/j.xphs.2018.07.005
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发表时间：
2019-01-01
影响因子：
3.8
通讯作者：
Tahir, Furqan
中科院分区：
文献类型：
--
作者：
Ottoboni, Sara;Price, Chris J.;Tahir, Furqan
缺乏商业实验室、中试和小生产规模的死端连续过滤和干燥装置，这是新活性药物成分（API）的连续药物生产工艺开发中的一个重大空白。为了将小规模药物分离从传统的分批Nutsche过滤向前推进到连续处理，与Alconbury韦斯顿有限公司合作开发了连续过滤干燥器原型装置（CFD20）。通过与手动最佳实践进行比较，评价了原型装置的性能，该手动最佳实践使用改良的Biotage VacMaster装置收集数据，并对API过滤和清洗进行了工艺理解。最终目的是将API浆液的化学和物理属性与设备和工艺参数联系起来，以改进API分离工艺。通过应用达西定律评估滤液流速来表征过滤性能，使用经典分析方法研究对产物晶体粒度分布和产物纯度的影响。2台设备的整体性能相似，表明原型CFD20可以匹配过滤和洗涤的最佳手动实验室实践，同时允许连续处理和实时数据记录。这一结果令人鼓舞，收集的数据为CFD20的发展提供了进一步的见解。(C)2019年美国药学协会（R）。爱思唯尔公司出版All rights reserved.
The lack of a commercial laboratory, pilot and small manufacturing scale dead end continuous filtration and drying unit it is a significant gap in the development of continuous pharmaceutical manufacturing processes for new active pharmaceutical ingredients (APIs). To move small-scale pharmaceutical isolation forward from traditional batch Nutsche filtration to continuous processing a continuous filter dryer prototype unit (CFD20) was developed in collaboration with Alconbury Weston Ltd. The performance of the prototype was evaluated by comparison with manual best practice exemplified using a modified Biotage VacMaster unit to gather data and process understanding for API filtration and washing. The ultimate objective was to link the chemical and physical attributes of an API slurry with equipment and processing parameters to improve API isolation processes. Filtration performance was characterized by assessing filtrate flow rate by application of Darcy's law, the impact on product crystal size distribution and product purity were investigated using classical analytical methods. The overall performance of the 2 units was similar, showing that the prototype CFD20 can match best manual lab practice for filtration and washing while allowing continuous processing and real-time data logging. This result is encouraging and the data gathered provides further insight to inform the development of CFD20. (C) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.