Mixing and Dissolution Processes of Pharmaceutical Bulk Materials in Stirred Tanks: Experimental and Numerical Investigations

Abstract

Numerical analysis of mixing and dissolution processes is becoming increasingly important for gaining a process understanding and thus optimizing the production. Due to the increasing costs and shortage of raw materials, in-silicotechniques are currently employed together with standard experimental analyses. Numerical simulations have proven to be a useful tool for understanding and optimizing industrial mixing problems. However, such simulations are still in the research phase. Although Computational Fluid Dynamics (CFD) is a well-developed and validated method, for more complex applications (e.g., industrial mixing)muchworkisstillrequiredtoobtainreliableresultsquicklyenough.Inthisworkwefocusedonthesimulationofmixingand dissolution of a bulk powder in a moderately viscous solution in an unbaffled stirred tank reactor typically used in the chemical and pharmaceutical industries. Estimations were made with regard to optimizing batch sizes, tank geometry, impeller type, and placement and process variables, such as the impeller agitation speed. In addition, the vortex formation of the liquid surface, the feeding position of the bulk powder, and the dissolution process of the solid particles that represent the bulk powder were manipulated.Finally,aquantitativecomparisonofdifferentstirringsystems andscale-up studieswas prepared. Thetime-dependent and turbulent flow of the mixture was studied by solving the Reynolds-averaged NavierStokes equations. The numerical predictions of the flow field were validated by means of high-speed camera images and particle image velocimetry postprocessing techniques.