Towards a digital twin of primary drying in lyophilization using coupled 3-D equipment CFD and 1-D vial-scale simulations

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Matej Zadravec , Efimia Metsi-Guckel , Blaz Kamenik , Johan Remelgas , Johannes Khinast , Nick Roscioli , Matthew Flamm , Harshil Renawala , Jeff Najarian , Atul Karande , Avik Sarkar
{"title":"Towards a digital twin of primary drying in lyophilization using coupled 3-D equipment CFD and 1-D vial-scale simulations","authors":"Matej Zadravec ,&nbsp;Efimia Metsi-Guckel ,&nbsp;Blaz Kamenik ,&nbsp;Johan Remelgas ,&nbsp;Johannes Khinast ,&nbsp;Nick Roscioli ,&nbsp;Matthew Flamm ,&nbsp;Harshil Renawala ,&nbsp;Jeff Najarian ,&nbsp;Atul Karande ,&nbsp;Avik Sarkar","doi":"10.1016/j.ejpb.2025.114662","DOIUrl":null,"url":null,"abstract":"<div><div>A digital twin of lyophilization units was developed to facilitate the scale-up of the lyophilization process from the laboratory to the commercial scale. Our focus was on ensuring successful technology transfer for manufacture of high-quality drug products. Traditionally, lyophilization models have been specific either to the equipment or to the vial. In this study, we integrated the equipment and the vial models in a way that they mutually influenced each other via boundary conditions (two-way coupling). We conducted two sets of calculations. Firstly, we performed steady-state simulations using Computational Fluid Dynamics (CFD) to simulate an ice slab test, which helped determine the equipment capability curve. Secondly, we carried out transient, coupled simulations using a coupled 3-D CFD and 1-D vial scale simulation model to mimic the primary drying phase in a lyophilizer. Using the coupled 3-D CFD and 1-D vial scale model, we were able to determine the product temperature, the sublimation rate and the cycle time based on the temporal and spatial conditions in the lyophilizer. The coupled approach was then applied to capture the effects of process disturbances and failure conditions in the lyophilizer, which enables a more robust process design.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"208 ","pages":"Article 114662"},"PeriodicalIF":4.4000,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Pharmaceutics and Biopharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0939641125000384","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

A digital twin of lyophilization units was developed to facilitate the scale-up of the lyophilization process from the laboratory to the commercial scale. Our focus was on ensuring successful technology transfer for manufacture of high-quality drug products. Traditionally, lyophilization models have been specific either to the equipment or to the vial. In this study, we integrated the equipment and the vial models in a way that they mutually influenced each other via boundary conditions (two-way coupling). We conducted two sets of calculations. Firstly, we performed steady-state simulations using Computational Fluid Dynamics (CFD) to simulate an ice slab test, which helped determine the equipment capability curve. Secondly, we carried out transient, coupled simulations using a coupled 3-D CFD and 1-D vial scale simulation model to mimic the primary drying phase in a lyophilizer. Using the coupled 3-D CFD and 1-D vial scale model, we were able to determine the product temperature, the sublimation rate and the cycle time based on the temporal and spatial conditions in the lyophilizer. The coupled approach was then applied to capture the effects of process disturbances and failure conditions in the lyophilizer, which enables a more robust process design.

Abstract Image

求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信