Design space of pharmaceutical processes using data-driven-based methods

Fani Boukouvala, Fernando J. Muzzio, Marianthi G. Ierapetritou

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Introduction: The identification and graphical representation of process design space are critical in locating not only feasible but also optimum operating variable ranges and design configurations. In this work, the mapping of the design space of pharmaceutical processes is achieved using the ideas of process operability and flexibility under uncertainty. Methods: For this purpose, three approaches are proposed which are based on different data-driven modeling techniques: response surface methodology, high-dimensional model representation, and kriging methodology. Using these approaches, models that describe the behavior of the process at different design configurations are generated using solely experimental data. The models are utilized in mixed integer non-linear programming formulations, where the optimum designs are identified for different combinations of input parameters within the operating parameter and material property ranges. Results: Based on this idea, by defining a desirable output range, the corresponding range of input variables that result to acceptable performance can be accurately calculated and graphically represented. Conclusions: The main advantages of the methodologies used in this work are, firstly, that there is no restriction by the lack of first-principle models that describe the investigated process and, secondly, that the models developed are computationally inexpensive. This work can also be used for the comparative analysis of the use of different surrogate-based methodologies for the identification of pharmaceutical process Design Space.

Original languageEnglish (US)
Pages (from-to)119-137
Number of pages19
JournalJournal of Pharmaceutical Innovation
Issue number3
StatePublished - Oct 2010

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery


  • Data-driven models
  • Design space mapping
  • High-dimensional model representations
  • Kriging
  • Pharmaceutical processes
  • Response surface


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