Automation in Pharmaceutical Crystallization

Crystallization is a key unit operation in the pharmaceutical industry for separation, purification, solid-form selection, and particle design. Yet, developing robust crystallization processes can be resource-intensive, since thermodynamics and kinetics both govern system behavior, resulting in numerous process parameters that must be optimized. Automation offers a powerful means to accelerate this development, but the very complexity that makes crystallization challenging─nonlinear responses, multiphase behavior, and a large design space, among other factors─also complicates automation. This review discusses how automation technologies are applied for resource-efficient crystallization process development, focusing on their contributions to the core process development activities: design space mapping, modeling, process control, optimization, and scale-up. Many automation tools─ranging from process analytical technology hardware to algorithmic experiment-selection and control software─are already widely used in crystallization, but typically in isolation. This review focuses on automation tools for pharmaceutical crystallization, emphasizing their role in accelerating process understanding, improving resource efficiency, enabling reproducible data generation, and supporting intelligent decision-making.

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Publication Details

Journal
Organic Process Research & Development
Published
2026-06-25
DOI
https://doi.org/10.1021/acs.oprd.6c00057
Primary Topic
Crystallization and Solubility Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

Automation in Pharmaceutical Crystallization

Daniel J. Griffin, Aniket Pradip Udepurkar, Giovanni Aprile, Cedric Devos et al.
Organic Process Research & Development
Crystallization and Solubility Studies
article

Automation in Pharmaceutical Crystallization

Daniel J. Griffin, Aniket Pradip Udepurkar, Giovanni Aprile, Cedric Devos, Torsten Stelzer, Allan S. Myerson, Peter Sagmeister, Francesco Destro, Richard D. Braatz, Hamza Youssef Ismail, Fateme Molajafari
article en

Abstract

Crystallization is a key unit operation in the pharmaceutical industry for separation, purification, solid-form selection, and particle design. Yet, developing robust crystallization processes can be resource-intensive, since thermodynamics and kinetics both govern system behavior, resulting in numerous process parameters that must be optimized. Automation offers a powerful means to accelerate this development, but the very complexity that makes crystallization challenging─nonlinear responses, multiphase behavior, and a large design space, among other factors─also complicates automation. This review discusses how automation technologies are applied for resource-efficient crystallization process development, focusing on their contributions to the core process development activities: design space mapping, modeling, process control, optimization, and scale-up. Many automation tools─ranging from process analytical technology hardware to algorithmic experiment-selection and control software─are already widely used in crystallization, but typically in isolation. This review focuses on automation tools for pharmaceutical crystallization, emphasizing their role in accelerating process understanding, improving resource efficiency, enabling reproducible data generation, and supporting intelligent decision-making.

Organic Process Research & Development
Amgen (United States) (US), University of Puerto Rico, Medical Sciences Campus (PR), University of Puerto Rico System (PR), Synergetics (Belgium) (BE), Institute of Crystallography (IT), Massachusetts Institute of Technology (US)
U.S. Food and Drug Administration
Decent work and economic growth
Openalex Percentile: Top 15%
Crystallization and Solubility Studies
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