Nucleation & Growth Kinetics for Combined Cooling & Antisolvent Crystallization in an MSMPR System
Estimating Solvent Dependency
During this presentation, Jennifer Schall discusses a method for evaluating solvent-dependent kinetics, then determining how the kinetic parameters are functions of solvent composition. Finally, crystallizer performance is predicted using these solvent-dependent kinetic parameters. These techniques are used by the Myerson Research Group at MIT.
Pharmaceutical companies are evaluating continuous processing to decrease costs and increase control. From a flow chemistry perspective, Mixed-Suspension, Mixed Product Removal (MSMPR) crystallizer are attractive. MSMPR crystallizers offer many advantages over batch crystallizers, including:
- Robust, Steady-State (SS) Operation
- Consistent Final Product and Quality
- Ability to Select Advantageous Operating Conditions With Beneficial Kinetics
- Control of Polymorphism, Purity, Morphology
Growth and nucleation kinetic parameters can be regressed simultaneously from SS MSMPR experimental data by combining population balance modeling with nonlinear regression. These crystallization kinetic parameters can have both temperature and solvent dependence. The four-step process that the Myerson Group at MIT uses to evaluate solvent-dependent kinetics for continuous crystallizer design is described during the presentation. A short case study is used to demonstrate the pitfalls of neglecting the solvent dependence of kinetic parameters, as well. The ultimate goal is to develop a continuous crystallization process for a commercial active pharmaceutical ingredient (API).
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Guest Presenter
Jennifer Moffitt Schall is an NSF Graduate Fellow at MIT, where she is pursuing both a PhD in Chemical Engineering and an MBA. In the Myerson Group, she studied antisolvent crystallization kinetics, focusing on how solvent mixtures play a role in crystal growth and nucleation rates. Before MIT, Jennifer graduated from Clemson University, obtaining a B.S. in Chemical Engineering with an emphasis on polymer science. She also spent three years working in the specialty chemicals industry, researching crystallization and filtration at Eastman Chemical Company as part of the Separations Engineering Research group.
