Gaining Fresh Insights into Crystallization in Process Chemistry

Crystallization is a common step used during the synthesis of organic compounds to isolate and purify the desired product. The adoption of simple Process Analytical Technologies (PAT) can provide new insights into crystallization procedures in process chemistry.

Process chemists commonly use crystallization during the synthesis of organic compounds. It enables improvement of intermediate synthesis steps – for impurity rejection and more efficient downstream filtration – and optimization of the final synthesis, allowing crystallization of the active ingredient under strict regulatory guidelines and with the desired bioavailability.

Optimization of this procedure requires scientists to have a good process understanding, which can be achieved by adopting Process Analytical Technologies (PAT). However, many PAT approaches can be complicated, limiting its adoption outside of specialist groups. In contrast, combining real-time microscopy with simple image analysis offers a straightforward technique suitable for all scientists.

This white paper was written for process chemists working in the pharmaceutical and chemical industries, and in academia. It focuses on process optimization, and demonstrates the ease with which relevant crystallization data can be obtained and analyzed without the need for specialist knowledge. It discusses the application of simple PAT tools to:

·         Identify polymorphs during crystallization development

·         Recognize and address oiling out (liquid-liquid phase separation)

·         Understand factors affecting crystal size, shape, and structure

·         Measure the influence of cooling rate on crystal size and shape