Harnessing Computational Fluid Dynamics (CFD) to Guide Reliable Scale-up of Pharmaceutical Processes

Successful scale-up of pharmaceutical batch and fed-batch processes in stirred vessels is largely a function of mixing that is governed by underlying hydrodynamics. This in turn is a strong function of various geometric and operational parameters, namely reactor diameter, fill level, impeller (type, number, size, location, and speed), the degree of baffling, feed location and addition rate along with physicochemical properties of the fluid and processing conditions (temperature and pressure). Reactor and impeller geometric configurations as well as vessel internals in laboratory reactors are significantly different than those at the pilot and commercial scales. Hence, it is crucial to understand the differences in the hydrodynamics across scales for accurate process scale-up. To this end, computational fluid dynamics (CFD) provides an efficient and reliable means for characterizing fluid flow.

We present general cases where the information obtained from CFD simulations carried out for a variety of configurations across scales can be effectively used to develop process understanding and guide reliable scale-up of batch and fed-batch processes.