Quantifying Nucleation and Growth Rates from Population Balance Models in Crystalline

  • Crystallization
  • 22 June 2023

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About the webinar

The development of digital twins for model-based crystallization process development is often limited by the associated material-intensive and time-intensive experimental screenings. Methods for measuring primary nucleation rates are well established and common practice for academic studies, however, methods for the measurement of secondary nucleation and crystal growth rates are often inconsistent due to differing strategies in the selection of supersaturation models, particle size measurement techniques, and investigated scales.

As a solution for the early characterization of crystallization processes, we will discuss a recent workflow of automated methods for the experimental screening, data analysis, and parameter estimation for secondary nucleation and crystal growth kinetics in solution crystallization. The methods, developed through a collaboration between Rowan University and Pfizer, have been integrated with common experimental protocols in the determination of induction times for primary nucleation, and with the use of commercially available tools that can be found in crystallization laboratories across academia and industry. These tools include a Technobis Crystalline as well as process simulation software. The workflow has been demonstrated for well-known organic and inorganic solutes, and some of these case studies will be discussed as examples.

The goal of these methods is not to obtain scalable kinetics (nucleation kinetics are strongly scale-dependent) or bypass process development at relevant scales, but to inform early process development and academic studies. Their value is on reproducibility between users and instruments, and the scalability of general crystallization trends (temperature effects, solvent effects, general solute behavior) rather than specific kinetic values. Potential applications in process development and academia, as well as the workflow’s limitations, was discussed during the talk.

Guest speaker

Dr. Gerard Capellades

Assistant Professor, Rowan University

Gerard Capellades is an Assistant Professor at Rowan University’s Department of Chemical Engineering, and head of the Crystallization Science & Pharmaceutical Engineering (CSPE) group. He obtained his PhD in 2017 from the Technical University of Denmark and Lundbeck, for his dissertation on “Design of Continuous Crystallizers for Production of Active Pharmaceutical Ingredients”. After completing his PhD, he conducted three years of postdoctoral research at the Massachusetts Institute of Technology (MIT), advised by Prof. Allan S. Myerson and Prof. Richard D. Braatz.

Most of Dr. Capellades’ prior research work involves the development and control of separation processes for pharmaceutical manufacturing, often combining theoretical studies with industrial applications. In his postdoctoral work, he had a leading role in two DARPA-funded projects, including the Pharmacy on Demand project. He also collaborated with Amgen for the development of digital twins for an end-to-end continuous manufacturing plant. Towards the end of his postdoctoral work, Dr. Capellades worked on the rapid development of crystallization processes for purification as part of DARPA’s Make-It program, and on the real time control of pharmaceutical drying operations in collaboration with Takeda and MIT’s Mechanical Engineering Department.

Currently, Dr. Capellades’ research group works on understanding the role of solvents and impurities on small-molecule crystallization kinetics, on the development of novel diagnostics and process design strategies for drug purification, the application of high-throughput experimentation and digital twins for crystallization process design, and on the design of sustainable solutions for water desalination using crystallization.