Research Article

Journal of Pharmaceutical Innovation

, Volume 8, Issue 1, pp 11-27

First online:

Computer-Aided Flowsheet Simulation of a Pharmaceutical Tablet Manufacturing Process Incorporating Wet Granulation

  • Fani BoukouvalaAffiliated withRutgers, The State University
  • , Anwesha ChaudhuryAffiliated withRutgers, The State University
  • , Maitraye SenAffiliated withRutgers, The State University
  • , Ruijie ZhouAffiliated withRutgers, The State University
  • , Lukasz MioduszewskiAffiliated withRutgers, The State University
  • , Marianthi G. IerapetritouAffiliated withRutgers, The State University
  • , Rohit RamachandranAffiliated withRutgers, The State University Email author 

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In this work, a dynamic flowsheet model for the production of pharmaceutical tablets through a continuous wet granulation process is developed. The unit operation models which are integrated to compose the process line form a hybrid configuration which is comprised of a combination of mechanistic models, population balance models, and empirical correlations, based on the currently available process knowledge for each individual component. The main objective of this study is to provide guidance in terms of the necessary steps which are required in order to move from the unit operation level to the simulation of an integrated continuous plant operation. Through this approach, not only significant process conditions for each individual process are identified but also crucial interconnecting parameters which affect critical material properties of the processed powder stream are distinguished. Through the integration of the dynamic flowsheet with a final component of tablet dissolution, the connection of the processing history of a set of powders which undergo wet granulation and are contained in each produced tablet to the release rate of the pharmaceutical ingredient is enabled. The developed flowsheet is used for the simulation of different operating scenarios and disturbances which are often encountered during operation for the assessment of their effects towards critical material attributes, product properties, and the operation of further downstream processes. Simulation results demonstrate that granulation and milling which control the particle size distribution of the processed powder mixture highly affect the hardness and dissolution of the produced tablets.


Pharmaceutical manufacturing Wet granulation Flowsheet simulation Population balance modeling