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An interactive tool has been developed to facilitate solvent selection, allowing consideration of chemical functionality, physical properties, regulatory concerns, and safety/health/environmental (SHE) impact. Appropriate solvents can be identified prior to screening experiments, and less desirable solvents can be replaced in established processes. Once a shortlist has been identified, the data can define experimental programs or else be exported to a molecular properties prediction tool to assess suitability through, e.g., solubility and partitioning.

A multidisciplinary approach covering synthetic, physical, and analytical chemistry, high-throughput experimentation and experimental design, process engineering, and solid-state chemistry is used to develop a large-scale (kilomole) Suzuki–Miyaura process. Working against clear criteria and targets, a full process investigation and optimization package is described highlighting how and why key decisions are made in the development of large-scale pharmaceutical processes.

A Lasentec FBRM probe was installed in a 450-L production unit and deployed to monitor the final three stages of the manufacturing process. Each step features a different type of crystallization: reactive, pH switch and cooling. In total over 100 batches were monitored. The probe detected ‘oiling out’ and seeding with agitation but did not detect ‘bearding’ or seeding without agitation. There was remarkable consistency from batch to batch, except for the first batches in some campaigns, which more closely resembled laboratory experiments. The challenge of interpreting Lasentec FBRM data in a production environment is addressed and compared with the alternative, in process control (IPC).