Power and fluid stress in disposable square stirred tank to streamline pharmaceutical process development

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Matteo Antognoli , Hessam Qeysari , Federico Alberini , Alessandro Paglianti , Pushpinder Singh , Andrea Albano
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引用次数: 0

Abstract

Single-use systems have quickly become a standard in biopharmaceutical manufacturing due to their superior operational efficiency, flexibility and cost-effectiveness. Despite their recent and intensive use, disposable stirred tanks are not fully understood and require further characterization. Single-use square stirred tanks may exhibit unusual power consumption that may impact drug substances and drug product critical quality attributes. In this work, we use torque measurements and particle image velocimetry to validate a Computational Fluid Dynamics model designed to elucidate the fluid dynamics in a transparent replica of the Flexel® LevMixer® 50 L. Using the validated model and exploiting the renormalization group k-ε two filling-volume-dependent behaviors were identified: (i) the Swirling flow regime, characterized by low power consumption per unit volume, and (ii) the Engulfed flow regime, which requires significantly higher power. For both regimes, fluid stress induced by the mechanical agitation from the impeller is thoroughly analyzed for intensity and frequency. A strong correlation between fluid stress and power consumption is demonstrated, with implications for pharmaceutical process development involving stress-sensitive drug substances and products. These findings, which correlate power consumption with fluid stress, can streamline drug development in the pharmaceutical industry and potentially support future development of new process analytical technologies to better control drug substance and drug product quality attributes.

Abstract Image

一次性方形搅拌槽的动力和流体应力以简化制药工艺开发。
由于其优越的操作效率、灵活性和成本效益,一次性使用系统已迅速成为生物制药制造的标准。尽管他们最近和密集的使用,一次性搅拌槽不完全了解,需要进一步表征。一次性使用的方形搅拌槽可能会出现不寻常的功率消耗,可能会影响原料药和药品的关键质量属性。在这项工作中,我们使用扭矩测量和粒子图像测速来验证计算流体动力学模型,该模型旨在阐明Flexel LevMixer 50 L透明复制品中的流体动力学。利用经过验证的模型并利用重整化群k-ε,确定了两种与填充体积相关的行为:(i)以单位体积功耗低为特征的旋流流态和(ii)吞没流态,这需要更高的功率。在两种情况下,对叶轮机械搅拌引起的流体应力的强度和频率进行了深入的分析。流体应力与电力消耗之间存在很强的相关性,这对涉及对压力敏感的药物物质和产品的制药工艺开发具有影响。这些发现将能量消耗与流体应力联系起来,可以简化制药行业的药物开发,并可能支持未来开发新的过程分析技术,以更好地控制原料药和药品质量属性。
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来源期刊
CiteScore
10.70
自引率
8.60%
发文量
951
审稿时长
72 days
期刊介绍: The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.
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