User-Friendly Population Balance Model with Data Integration for the Digital Design of Crystallization Systems | AIChE

User-Friendly Population Balance Model with Data Integration for the Digital Design of Crystallization Systems


Industry-wide precompetitive collaborations have been increasingly promoted by the pharmaceutical industry [1]. The mission of the Enabling Technologies Consortium (ETC) is to enable rapid, pre-competitive collaborative development of new enabling technologies for the pharmaceutical industries. Precompetitive collaborations have advantages beyond the financial benefits (of leveraged risk) to their participants, as they can also be used to deliver products with tailored features valuable to their users in contrast to the development of tools with broad features generally applicable to all industries but not necessarily ideal for any of them. For many ETC projects, future users are directly involved in product development, at times serving as high level technical advisors and beta-testers. In this work present the product of one of the first ETC projects, which has resulted in a new population balance model (PBM) based interactive, user-friendly crystallization software for pharmaceutical research and development. The key scope of the Crystallization Simulation and Visualisation (CrySiV) software tool is to perform process modeling and simulation of industrial crystallization processes by regressing model parameters from the experimental data [2]. Consequently, through in-silico experiments the software can enable better understanding of key correlations between critical quality attributes (CQAs) and critical process parameters (CPPs) and ultimately promote the efficient and rapid digital design of crystallization systems. CrySiV is aimed to merge the state-of-the-art in crystallization modeling, simulation, parameter estimation and optimization into a user-friendly interface. It allows efficient input of typical experimental data, guides the user to perform efficient parameter estimation and enables in silico investigations and digital design of crystallization and integrated crystallization and wet-milling systems, for both batch and continuous processes. The talk describes the key features of the CrySiV software, introduces the 1D and 2D PBM framework used in the model and provide examples of how the tool can facilitate rapid crystallization design in the case of a batch combined cooling, antisolvent crystallization, investigate transition of batch to continuous crystallization processes and perform the digital design of an integrated crystallization wet milling system. The successful examples demonstrate the benefits of in silico design of experiments and digital design of crystallization systems, through saving experimental time and material, and speeding up industrial crystallization development, thereby CrySiV promotes the broader adoption of digital technologies in modern pharmaceutical manufacturing.

[1] J. Welch, C.; M. Hawkins, J.; Tom, J., Precompetitive Collaboration on Enabling Technologies for the Pharmaceutical Industry, Org. Process Res. & Dev., 18 (4), 481–487, 2014.

[2] B. Szilagyi, W.-L. Wu, A. Eren, J. Mackey, S. Kshirsagar, E. Szilagyi, I. Ostergaard, K. Sinha, L. Mlinar, D. Pohlman, J. Chen, N. Nere, B. Moussa, M. Lovette, S. Black, A. Jawor-Baczynska, H. Li, B.-S. Yang, E. Irdam, D. Patience, R. McKeown, D. Juboor, M. Ketchum, D. Green, C. Polster, C. Burcham, D. Jarmer, J. Miles Merritt, L. Codan, J. Schoell, A. Cote, E. Sirota, Y.C. Liu, K. Girard, S. Kulkarni, Y. Yang, J. L. Quon, Z. K. Nagy, Cross-pharma collaboration for the development of a simulation tool for the model based digital design of pharmaceutical crystallization processes (CrySiV), Cryst. Growth & Des., 21 (11), 6448-6464, 2021.