White Paper

Crystallization in Process Chemistry

White Paper

Applying Simple PAT Tools

In process chemistry, crystallization is a common step used during the synthesis of organic compounds to isolate and purify the desired product, and chemists now spend more time developing better crystallization processes. Intermediate synthesis steps can be improved with crystallization for impurity rejection and more efficient downstream filtration.  Also, the final synthesis step can be optimized with crystallization of the active ingredient under strict regulatory guidelines and with the desired bioavailability.

By adopting simple Process Analytical Technologies (PAT), new insights into crystallization can be found in process chemistry - without requiring a high level of expertise.  One PAT technology, real-time microscopy, provides high quality images and videos of crystals and crystal structures inline as process conditions are changing.

This white paper discusses how to apply simple PAT tools to crystallization in process chemistry to:

1.      Identify Polymorphs During Crystallization Development

2.      Recognize and Address Oiling Out (Liquid-Liquid Phase Separation)

3.      Understand Factors Affecting Crystal Size, Shape, and Structure

4.      Measure the Influence of Cooling Rate on Crystal Size and Shape

This white paper was written for process chemists working in the pharmaceutical and chemical industries as well as academia.

Crystallization is a unique unit operation that offers scientists a method to isolate and purify products in a single step.  The pressure to deliver optimized crystal products with the desired attributes is increasing and scientists need to obtain better process understanding to support thier optimization efforts.  Many PAT tools suitable for supporting the development of crystallization processes are valuable, but can be complicated enough to limit their adoption outside dedicated groups of specialists.  Real-time microscopy combined with simple image analysis, offers an opportunity for every scientist to begin using PAT to design, analyze, and control crystallization processes as part of the PAT framework.

This paper focuses on process optimization and demonstrates the ease with which relavant crystallization data can be obtained and analyzed - without any special expertise.  This results in crystallization processes that will deliver the required critical quality attributes consistently at every scale required in process chemistry.