Integrated modelling of a continuous direct compression tablet manufacturing process: A production scale case study by S.C. Galbraith *, B. Cha, Z. Huang, S. Park, H. Liu, S. Yoon of Department of Chemical Engineering, University of Massachusetts Lowell; R.F. Meyer, S. Hurley, F. Zhang-Plasket of Pharmaceutical Commercialization Technology, Merck & Co., Inc; M.H. Flamm of Applied Mathematics and Modeling, Scientific Modeling Platforms, Merck & Co., Inc,.
Published in Powder Technology, Elsevier.
|Shaun C. Galbraith||Bumjoon Cha||Zhuangrong Huang||Seoyoung Park||Huolong Liu|
|Robert F. Meyer||Matthew H. Flamm||Samantha Hurley||Fan Zhang-Plasket||Seongkyu Yoon|
A flowsheet model for a continuous direct compression tableting process is developed and applied to process data generated at production scale. The model contains powder feeding, blending and tablet compaction unit operations. The dataset was provided by Merck & Co., Inc., Kenilworth, NJ USA using a GEA ConsiGma™ continuous direct compression process designed for approximately 50 kg/h throughput using a six ingredient, potentially commercial, formulation. A tanks-in-series methodology is used to model the transport of powders through the blending units and a number of tablet compaction equations are selectable which can illustrate how upstream changes in composition are propagated to tablet properties. The flowsheet model performed well based on the available dataset with accurate predictions of API concentration and tablet hardness. Monte Carlo simulations were used along with the flowsheet model to investigate the contribution of feeder flowrate variability to measurement noise and the sensitivity of tablet hardness to process parameters and material properties.
Shaun C. Galbraith*
Dr. Shaun Galbraith is a Research Engineer at the University of Massachusetts Lowell. His research focuses on developing process models for particulate systems and crystallization. The scope of his research ranges from small and large molecule pharmaceutical manufacturing to nutrient recovery from wastewater addressing the issue of phosphorus sustainability. He also has done fundamental experimental work investigating the phenomena of crystal growth rate dispersion. He is currently working on developing flowsheet models for solid drug manufacturing processes to be used in case studies with project collaborators and translating those models to biomanufacturing. He received his Bachelor of Engineering and Doctor of Philosophy from James Cook University in Queensland Australia.
Dr. Bumjoon Cha was a research engineer at the University of Massachusetts Lowell. His research at UML focused on tablet coating and drying dynamics. Following the completion of the grants he was working on at UML, he returned to Korea as a process modeling expert at Samsung Biologics.
Mr. Zhuangrong Huang is a PhD candidate at the University of Massachusetts Lowell where part of is work involved process modeling of oral-dosage tablet manufacturing focusing on tablet compaction. He recently defending his PhD thesis and will soon graduate to take a position at Bristol Myers Squibb.
Dr. Seongkyu Park was a PhD candidate at the University of Massachusetts Lowell where part of her work involved process modeling of oral-dosage tablet manufacturing focusing on roller compaction. A paper she produced from this work was the runner-up in the 2018 PSE Model-Based Innovation prize. Following her PhD studies she worked in process development at Bristol Myers Squibb and is currently a Postdoctoral Fellow at Tufts University in Massachusetts working on applications of metabolomics.
Dr. Huolong Liu is currently working as research engineer in the department of chemical engineering, University of Massachusetts Lowell. My research focus is on Pharmaceutical modelling and simulation. Research covers pharmaceutical process modelling, model optimization and control strategy design, and CFD simulation on multiphase flow. I am currently working on developing integrated flowsheet modeling platform of a continuous wet granulation tablet manufacturing system, including twin screw granulator, fluid bed dryer, mill and tablet press.
Robert F. Meyer
Matthew H. Flamm
Dr. Seongkyu Yoon is a Professor in the department of chemical engineering, and the Ward Endowed Professor in Biomedical Sciences, at the University of Massachusetts Lowell. Currently he is working as a NSF/IUCRC, AMBIC (Advanced Mammalian Biomanufacturing Innovation Center) UMass Site Director, and leading Biomanufacturing Innovation Institute. He runs systems biology group conducting research in systems biotechnology, life science informatics, and regulatory sciences with goals to develop an innovative biomanufacturing platform of protein/cell/gene biotherapeutics. Dr. Yoon worked at Umetrics (Now Satorius) and Biogen before he joined UMass. He has PhD from McMaster University (Hamilton Canada).
* Submitting author