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Dynamic flowsheet model development and sensitivity analysis of a continuous pharmaceutical tablet manufacturing process using the wet granulation route

(2019) PROCESSES. 7(4).
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Abstract
In view of growing interest and investment in continuous manufacturing, the development and utilization of mathematical model(s) of the manufacturing line is of prime importance. These models are essential for understanding the complex interplay between process-wide critical process parameters (CPPs) and critical quality attributes (CQAs) beyond the individual process operations. In this work, a flowsheet model that is an approximate representation of the ConsiGma<mml:semantics>TM</mml:semantics>-25 line for continuous tablet manufacturing, including wet granulation, is developed. The manufacturing line involves various unit operations, i.e., feeders, blenders, a twin-screw wet granulator, a fluidized bed dryer, a mill, and a tablet press. The unit operations are simulated using various modeling approaches such as data-driven models, semi-empirical models, population balance models, and mechanistic models. Intermediate feeders, blenders, and transfer lines between the units are also simulated. The continuous process is simulated using the flowsheet model thus developed and case studies are provided to demonstrate its application for dynamic simulation. Finally, the flowsheet model is used to systematically identify critical process parameters (CPPs) that affect process responses of interest using global sensitivity analysis methods. Liquid feed rate to the granulator, and air temperature and drying time in the dryer are identified as CPPs affecting the tablet properties.
Keywords
model integration, flowsheet modeling, sensitivity analysis, continuous manufacturing, wet granulation, DISTRIBUTIONS, OPTIMIZATION, SIMULATION, BIOMATH

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Chicago
Metta, Nirupaplava, Michael Ghijs, Elisabeth Schäfer, Ashish Kumar, Philippe Cappuyns, Ivo Van Assche, Ravendra Singh, et al. 2019. “Dynamic Flowsheet Model Development and Sensitivity Analysis of a Continuous Pharmaceutical Tablet Manufacturing Process Using the Wet Granulation Route.” Processes 7 (4).
APA
Metta, N., Ghijs, M., Schäfer, E., Kumar, A., Cappuyns, P., Van Assche, I., Singh, R., et al. (2019). Dynamic flowsheet model development and sensitivity analysis of a continuous pharmaceutical tablet manufacturing process using the wet granulation route. PROCESSES, 7(4).
Vancouver
1.
Metta N, Ghijs M, Schäfer E, Kumar A, Cappuyns P, Van Assche I, et al. Dynamic flowsheet model development and sensitivity analysis of a continuous pharmaceutical tablet manufacturing process using the wet granulation route. PROCESSES. 2019;7(4).
MLA
Metta, Nirupaplava et al. “Dynamic Flowsheet Model Development and Sensitivity Analysis of a Continuous Pharmaceutical Tablet Manufacturing Process Using the Wet Granulation Route.” PROCESSES 7.4 (2019): n. pag. Print.
@article{8618449,
  abstract     = {In view of growing interest and investment in continuous manufacturing, the development and utilization of mathematical model(s) of the manufacturing line is of prime importance. These models are essential for understanding the complex interplay between process-wide critical process parameters (CPPs) and critical quality attributes (CQAs) beyond the individual process operations. In this work, a flowsheet model that is an approximate representation of the ConsiGma<mml:semantics>TM</mml:semantics>-25 line for continuous tablet manufacturing, including wet granulation, is developed. The manufacturing line involves various unit operations, i.e., feeders, blenders, a twin-screw wet granulator, a fluidized bed dryer, a mill, and a tablet press. The unit operations are simulated using various modeling approaches such as data-driven models, semi-empirical models, population balance models, and mechanistic models. Intermediate feeders, blenders, and transfer lines between the units are also simulated. The continuous process is simulated using the flowsheet model thus developed and case studies are provided to demonstrate its application for dynamic simulation. Finally, the flowsheet model is used to systematically identify critical process parameters (CPPs) that affect process responses of interest using global sensitivity analysis methods. Liquid feed rate to the granulator, and air temperature and drying time in the dryer are identified as CPPs affecting the tablet properties.},
  articleno    = {234},
  author       = {Metta, Nirupaplava and Ghijs, Michael and Schäfer, Elisabeth and Kumar, Ashish and Cappuyns, Philippe and Van Assche, Ivo and Singh, Ravendra and Ramachandran, Rohit and De Beer, Thomas and Ierapetritou, Marianthi and Nopens, Ingmar},
  issn         = {2227-9717},
  journal      = {PROCESSES},
  keywords     = {model integration,flowsheet modeling,sensitivity analysis,continuous manufacturing,wet granulation,DISTRIBUTIONS,OPTIMIZATION,SIMULATION,BIOMATH},
  language     = {eng},
  number       = {4},
  pages        = {35},
  title        = {Dynamic flowsheet model development and sensitivity analysis of a continuous pharmaceutical tablet manufacturing process using the wet granulation route},
  url          = {http://dx.doi.org/10.3390/pr7040234},
  volume       = {7},
  year         = {2019},
}

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