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Iterative Model Based Experimental Design for Spherical Agglomeration Processes
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  • Kanjakha Pal,
  • Botond Szilagyi,
  • Christopher Burcham,
  • Daniel Jarmer,
  • Zoltan Nagy
Kanjakha Pal
Purdue University

Corresponding Author:[email protected]

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Botond Szilagyi
Purdue University
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Christopher Burcham
Eli Lilly and Company
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Daniel Jarmer
Eli Lilly and Company
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Zoltan Nagy
Purdue University
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Abstract

Spherical agglomeration (SA) is a process intensification (PI) strategy, which can reduce the number of unit operations in pharmaceutical manufacturing. SA merges drug substance crystallization with drug product wet granulation, reducing capital and operating costs. However, SA is a highly nonlinear process, thus for its efficient operation model-based design and control strategies are beneficial. These require the development of a high-fidelity process model with appropriately estimated parameters. There are two major problems associated with the development of a high-fidelity process models – (i) selection of the appropriate model corresponding to the underlying process mechanisms, and (ii) accurate estimation of the parameters. This work focuses on the identification of the best fitting model that correlates with experimental observations using cross-validation experiments. Further, an Iterative Model Based Experimental Design (IMED) strategy is developed, which uses D-optimal experimental design criterion to minimize the number of experiments necessary to obtain accurate parameter estimates.
10 Mar 2020Submitted to AIChE Journal
03 Apr 2020Submission Checks Completed
03 Apr 2020Assigned to Editor
10 Apr 2020Reviewer(s) Assigned
13 Jul 2020Editorial Decision: Revise Major
13 Oct 20201st Revision Received
23 Oct 2020Submission Checks Completed
23 Oct 2020Assigned to Editor
27 Oct 2020Reviewer(s) Assigned
17 Dec 2020Editorial Decision: Accept