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-silico" techniques 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) much work is still required to obtain reliable results quickly enough. In this work we focused on the simulation of mixing and 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, a quantitative comparison of different stirring systems and scale-up studies was prepared. The time-dependent and turbulent flow of the mixture was studied by solving the Reynolds-averaged NavierÀStokes equations. The numerical predictions of the flow field were validated by means of high-speed camera images and particle image velocimetry postprocessing techniques.

A Comparison of Mass Transfer Coefficients between Rotating Magnetic Field Mixer and Stirred Tank Reactor

“…The dissolution process of a solid body in a liquid can occur spontaneously or it can be intensified. One of the simplest methods of the mass transfer intensification is dissolution in mechanical mixers, i.e., apparatus with moving impellers [27,28]. Using the mechanical impeller should provide increase of the liquid turbulence, particularly at the boundary of the phases.…”

The Influence of Process Parameters on the Properties of PLGA‐Microparticles Produced by the Emulsion Extraction Method

“…The geometry of the injection glass tube was not considered, that is, the flow around the submerged glass tube during emulsion injection was disregarded, in agreement with the experimental practice prescribing that the glass tube should be removed from the vessel after dosing the emulsion. Further details of the numerical approach and its experimental validation can be found in the literature …”

“…Due to the short Stokesian relaxation time of the particles, the velocity fluctuations dominate the transport processes across the particle interface. Details of the turbulent dispersion modeling can be found in the literature . Because the concentration of the emulsion droplets in the stirred tank was low, it was appropriate to use one‐way momentum coupling between the continuous fluid and the parcels.…”

Solid Dissolution and Liquid Mixing in Turbulent Stirred Tanks

“…The investigations carried out so far in this field have led to useful correlations for the prediction of the mass transfer coefficient . More recently, studies have started being based on local hydrodynamics measurement and prediction methods with the final aim of devising robust and comprehensive modeling tools for the design and optimization of industrial operations.…”