Process Analytical Technology: An Investment in Process Knowledge

Process analytical technology (PAT) is fast becoming an integral part of many active pharmaceutical ingredient (API) production facilities. The incorporation of early PAT devices, such as pH probes for example, was shown to increase process efficiency and safety by acting on data in real time and by eliminating sampling. PAT applications, such as online redox, NIR, and sophisticated particle size analysis, increase (in real time) detailed knowledge of processes, thus affording increased robustness and greater straight-through processing (right-first-time) opportunities. Modern developments in analytical technologies provide chemical and analytical insights for all types of chemical reactions and process monitoring such as drying, distillations, crystallizations, hydrogenations, and others. This article will discuss two applications; each is very different from the other. The first application, redox monitoring, is a traditional PAT application used to monitor differences in the oxidation state of two reaction constituents. Our discussion will describe an oxidation/reduction (redox) application used to monitor the reduction of excess bromine with sodium bisulfite using an online probe. The second application is crystallization and granulation monitoring using a Lasentec Focused Beam Reflectance Measurement (FBRM) instrument for the optimization of a crystallization and granulation process in manufacturing (reference information is publicly available on this equipment; visit the Mettler-Toledo website at: http:// www.lasentec.com/method_of_measurement.html).