A Review of Computational Fluid Dynamics (CFD) Simulations of Mixing in the Pharmaceutical Industry

Abstract

Due to the increasing computational power and availability of advanced commercial, as well as open-source computational fluid dynamics (CFD) software, performing CFD simulations is becoming more accessible and its use has expanded into many industrial sectors. For the pharmaceutical industry, the topic of mixing is especially of interest, since it is a common unit operation in pharmaceutical processes and empirical and semi-empirical correlations for predicting the hydrodynamic characteristics inside a batch mixing vessel do not consider the complete three-dimensional geometry of the vessel and impeller. This is important in processes such as crystallization, dissolution, compounding, and cellular production in bioreactors, and the obtained information can aid in the selection of the mixer geometry, the choice of mixing speed and for achieving comparable scale-up/down operation of laboratory and industrial mixing vessels. The pharmaceutical industry is not keen on publishing their research and the details of their technology, so the available literature is limited. In this mini review, publications, in which CFD simulations of the mixing process were performed for real pharmaceutical cases are presented, the obtained results are discussed and the software, modeling techniques and methods and their comparisons to measurements are highlighted.

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

“…Solution viscosity is a critical attribute for the development of high-concentration protein formulations, as an elevated viscosity (>30 cP) can significantly impact the pressure and flow in various unit operations such as filtration, ultrafiltration-diafiltration, and filling, 95 , 96 as well as limit the development of devices for drug administration (e.g., auto-injectors and pre-filled syringes). 186 From a physicochemical standpoint, it has been proposed that the presence of transient protein clusters is the root cause of high viscosity in protein solutions, which is in turn driven by protein–protein interactions.…”

Integration Approaches to Model Bioreactor Hydrodynamics and Cellular Kinetics for Advancing Bioprocess Optimisation

“…Cell culture dynamics, metabolism and product glycosylation have been modelled in the past using mechanistic models [ 56 , 57 , 58 ], statistical models [ 59 , 60 , 61 ], and hybrid models [ 61 , 62 ]. The application of CFD for hydrodynamic characterisation and scale-up and CRK for cell metabolism modelling has been extensively reviewed recently [ 63 , 64 , 65 , 66 ]. In this review, the focus is on the research articles wherein both the CFD and CRK modelling approaches have been integrated as this strategy has the potential to optimise the whole bioprocess rather than optimisation advances in just unit steps involved in bioprocessing.…”