(231b) Slurry Milling As a Tool to Improve Particle Properties to Avoid Slurry Thickening, Impurity/Residual Solvent Rejection and Improved Physical Properties

Crystallization is the defacto unit operation for controlling purification and particle properties. As part of the process, slurry milling is routinely employed for controlling multiple quality attributes ranging from particle size, filterability, agglomeration control etc. Herein, we present a case study about using method of moments based crystallization modeling along with experiments with slurry mill to control the size and shape of particles, [1, 2] control the viscosity of the slurry to avoid clogging risk and mitigate high residual solvents in the final dry API. We outline a general workflow of how the study was conducted for an accelerated timeline of development. [3, 4] We discuss the value of scale up related properties affecting slurry thickening and physical properties like PSD and aspect ratio

References

1. Meng, W., et al., Effective control of crystal size via an integrated crystallization, wet milling, and annealing recirculation system. Organic Process Research & Development, 2020. 24(11): p. 2639-2650.
2. Agrawal, S., et al., Use of automation, dynamic image analysis, and process analytical technologies to enable data rich particle engineering efforts at the Drug Substance/Drug Product interface: A case study using Lovastatin. Chemical Engineering Research and Design, 2024. 205: p. 578-590.
3. Patil, S., et al., Solvent Entrapment of BI 763963 by Solid Solution Formation. Crystal Growth & Design, 2025.
4. Agrawal, P., et al., Case studies in the application of a workflow-based crystallization design for optimized impurity rejection in pharmaceutical development. Organic Process Research & Development, 2023. 27(4): p. 610-626.