Journal of Pharmaceutical Innovation

, Volume 8, Issue 2, pp 131–145 | Cite as

Surrogate-Based Optimization of Expensive Flowsheet Modeling for Continuous Pharmaceutical Manufacturing

  • Fani Boukouvala
  • Marianthi G. Ierapetritou
Research Article


Simulation-based optimization is a research area that is currently attracting a lot of attention in many industrial applications, where expensive simulators are used to approximate, design, and optimize real systems. Pharmaceuticals are typical examples of high-cost products which involve expensive processes and raw materials while at the same time must satisfy strict quality regulatory specifications, leading to the formulation of challenging and expensive optimization problems. The main purpose of this work was to develop an efficient strategy for simulation-based design and optimization using surrogates for a pharmaceutical tablet manufacturing process. The proposed approach features surrogate-based optimization using kriging response surface modeling combined with black-box feasibility analysis in order to solve constrained and noisy optimization problems in less computational time. The proposed methodology is used to optimize a direct compaction tablet manufacturing process, where the objective is the minimization of the variability of the final product properties while the constraints ensure that process operation and product quality are within the predefined ranges set by the Food and Drug Administration.


Surrogate-based optimization Simulation-based optimization Kriging Pharmaceutical manufacturing Flowsheet simulation 



The authors would like to acknowledge the funding provided by the ERC (NSF-0504497, NSF-ECC 0540855).


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Chemical and Biochemical EngineeringRutgers UniversityPiscatawayUSA

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