{"title":"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。","authors":"Matteo Antognoli , Hessam Qeysari , Federico Alberini , Alessandro Paglianti , Pushpinder Singh , Andrea Albano","doi":"10.1016/j.ijpharm.2025.126243","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126243"},"PeriodicalIF":5.2000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Power and fluid stress in disposable square stirred tank to streamline pharmaceutical process development\",\"authors\":\"Matteo Antognoli , Hessam Qeysari , Federico Alberini , Alessandro Paglianti , Pushpinder Singh , Andrea Albano\",\"doi\":\"10.1016/j.ijpharm.2025.126243\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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.</div></div>\",\"PeriodicalId\":14187,\"journal\":{\"name\":\"International Journal of Pharmaceutics\",\"volume\":\"685 \",\"pages\":\"Article 126243\"},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Pharmaceutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378517325010804\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378517325010804","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Power and fluid stress in disposable square stirred tank to streamline pharmaceutical process development
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.
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.