An integrated approach for dynamic flowsheet modeling and sensitivity analysis of a continuous tablet manufacturing process

Manufacturing of powder-based products is a focus of increasing research in the recent years. The main reason is the lack of predictive process models connecting process parameters and material properties to product quality attributes. Moreover, the trend towards continuous manufacturing for the pro...

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Bibliographic Details
Published in:Computers & chemical engineering 2012-07, Vol.42, p.30-47
Main Authors: Boukouvala, Fani, Niotis, Vasilios, Ramachandran, Rohit, Muzzio, Fernando J., Ierapetritou, Marianthi G.
Format: Article
Language:English
Subjects:
Applications of mathematics to chemical engineering. Modeling. Simulation. Optimization
Applied sciences
Chemical engineering
Computer simulation
Dynamic flowsheet simulation
Dynamic tests
Dynamics
Exact sciences and technology
Fluctuation
Mathematical models
Mechanical engineering. Machine design
Pharmaceutical manufacturing
Pharmaceuticals
Population balance modeling
Sensitivity analysis
Tablets
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Summary:Manufacturing of powder-based products is a focus of increasing research in the recent years. The main reason is the lack of predictive process models connecting process parameters and material properties to product quality attributes. Moreover, the trend towards continuous manufacturing for the production of multiple pharmaceutical products increases the need for model-based process and product design. This work aims to identify the challenges in flowsheet model development and simulation for solid-based pharmaceutical processes and show its application and advantages for the integrated simulation and sensitivity analysis of two tablet manufacturing case studies: direct compaction and dry granulation. The developed flowsheet system involves a combination of hybrid, population balance and data-based models. Results show that feeder refill fluctuations propagate downstream and cause fluctuations in the mixing uniformity of the blend as well as the tablet composition. However, this effect can be mitigated through recycling. Dynamic sensitivity analysis performed on the developed flowsheet, classifies the most significant sources of variability, which are material properties such as mean particle size and bulk density of powders.
ISSN:0098-1354
1873-4375
DOI:10.1016/j.compchemeng.2012.02.015