Fernando J. Muzzio

Using time-dependent RPM to enhance mixing in stirred vessels

Abstract Mixing under low to moderate Reynolds numbers is investigated experimentally in a stirred tank. An acid-base neutralization reaction and a pH indicator are used to reveal the existence, location, and size of segregated regions in the flow. Such regions are observed for both unbaffled and baffled vessels stirred by either radial or axial flow impellers. These segregated regions have a complex internal structure consistent of several families of helical filaments wrapped around a central torus. It is demonstrated that the segregated regions are readily destroyed through the use of time-dependent RPM.

Powder technology in the pharmaceutical industry: the need to catch up fast

Pharmaceutical product development and manufacturing, which is largely an exercise in particle technology, is in serious need of technical upgrading. In this article, an overview of the current state of the art is provided, along with a discussion of expected research trends and their economic and societal impacts. In particular, the anticipated role of nanotechnology is discussed in some detail.

Experimentally validated computations of flow, mixing and segregation of non-cohesive grains in 3D tumbling blenders

Granular mixing is a vital operation in food, chemical, and pharmaceutical industries. Although the tumbling blender is by far the most common device used to mix grains, surprisingly little is known about mixing or segregation in these devices. In this paper, we report the first fully three-dimensional (3D) particle dynamics simulations of granular dynamics in two standard industrial tumbling blender geometries: the double-cone and the V-blender. Simulations for both monodisperse and bidisperse (segregating) grain sizes are performed and compared with experiment. Mixing and transport patterns are studied, and we find in both tumblers that the dominant mixing mechanism, azimuthal convection, contends against the dominant bottleneck, axial dispersion. The dynamics of blending, on the other hand, differs dramatically between the two tumblers: flow in the double-cone is nearly continuous and steady, while flow in the V-blender is intermittent and consists of two very distinct processes.

Chaos, Symmetry, and Self-Similarity: Exploiting Order and Disorder in Mixing Processes

Fluid mixing is a successful application of chaos. Theory anticipates the coexistence of order and disorder—symmetry and chaos—as well as self-similarity and multifractality arising from repeated stretching and folding. Experiments and computations, in turn, provide a point of confluence and a visual analog for chaotic behavior, multiplicative processes, and scaling behavior. All these concepts have conceptual engineering counterparts: examples arise in the context of flow classification, design of mixing devices, enhancement of transport processes, and controlled structure formation in two-phase systems.

Quantification of mixing in aperiodic chaotic flows

Abstract Most previous studies of mixing in deterministic flows have focused on time-periodic or spatially-periodic flows. In contrast, mixing processes in aperiodic flows have been considerably less studied. Four procedures are used in this paper to generate well-characterized aperiodic flows. These procedures are applied to the cavity flow and to a two-dimensional mapping with a sinusoidal velocity profile. Mixing in periodic and aperiodic flows is quantitatively compared. Since most of the available analytical tools developed in the context of periodic systems (Poincare sections, periodic points and their associated manifolds) are poorly suited for the analysis of aperiodic systems, comparisons are based on measures, such as the structure and statistics of the stretching field and the rate of tracer spreading, that apply to both periodic and aperiodic systems. Aperiodicity enhances mixing enormously. Aperiodic perturbations generate widespread chaos under conditions where periodic flows generate minimal or no chaos. The average rate of stretching of material elements can be increased several orders of magnitude in brief intervals corresponding to just 10–20 periods of the periodic flow. The spatial distribution of stretching is much more uniform for aperiodic systems than for periodic ones, and tracers spread much more rapidly and uniformly.

Experimental and computational investigation of the laminar flow structure in a stirred tank

The laminar flow structure inside an unbaffled stirred tank generated by a 6-blade radial flow impeller was characterized using flow visualization experiments, particle imaging velocimetry (PIV) experiments, and computational fluid dynamics (CFD) simulations. As expected from a previous study (Lamberto et al., 1996), the dominant flow structures in the system were two ring vortices above and below the impeller. These secondary circulation regions were segregated from the bulk of the flow and, for low impeller Reynolds numbers (5<Re<100), their positions and size were found to depend on Re and on the position of the impeller blades. The pumping capacity and circulation flow of the impeller were quantified and results indicate that the circulation flow was approximately 4 times the pumping capacity of the impeller.

An integrated approach for dynamic flowsheet modeling and sensitivity analysis of a continuous tablet manufacturing process

Abstract Manufacturing of powder-based products is a focus of increasing research in the recent years. The main reason is the lack of predictive process models connecting process parameters and material properties to product quality attributes. Moreover, the trend towards continuous manufacturing for the production of multiple pharmaceutical products increases the need for model-based process and product design. This work aims to identify the challenges in flowsheet model development and simulation for solid-based pharmaceutical processes and show its application and advantages for the integrated simulation and sensitivity analysis of two tablet manufacturing case studies: direct compaction and dry granulation. The developed flowsheet system involves a combination of hybrid, population balance and data-based models. Results show that feeder refill fluctuations propagate downstream and cause fluctuations in the mixing uniformity of the blend as well as the tablet composition. However, this effect can be mitigated through recycling. Dynamic sensitivity analysis performed on the developed flowsheet, classifies the most significant sources of variability, which are material properties such as mean particle size and bulk density of powders.

Spontaneous chaotic granular mixing

There are several types of instabilities in fluid mechanics that lead to spontaneous chaotic mixing and intricate patterns. Classical examples include the Kelvin–Helmholtz instability in shear layers, the instability of Taylor–Couette flow between rotating cylinders and the Rayleigh-Bénard instability in thermal convection. More recently, a variety of two- and three-dimensional chaotic mixing phenomena have been observed in other geometries. Mixing in granular flows, unlike that in stirred fluids, is thought to be diffusive—although periodic forcing has been used to enhance granular mixing, spontaneous chaotic granular mixing has not previously been reported. Here we report the observation of chaotic granular mixing patterns in simple cylindrical tumblers partially filled with fine grains. The patterns form spontaneously when sufficiently fine grains (≲300 µm diameter) are blended. We identify the mechanism by which the chaotic patterns are produced: a periodic stick–slip behaviour occurs in the shear layer separating static and flowing regions of grains. This causes weakly cohesive grains to mix at rates overwhelmingly exceeding those achievable for previously studied freely flowing grains.

Sampling and characterization of pharmaceutical powders and granular blends

We use a variety of experimental results to illustrate issues and challenges involved in the sampling and characterization of pharmaceutical mixtures. Accurate and reliable characterization of granular mixtures is hindered by both the complexity of granular systems and the lack of validated and reliable sampling technology and techniques. Both sampling tools and sampling protocols are critically important for accurate characterization. Using cohesive and free-flowing powders and four thief probe designs, we reveal a large potential for extremely misleading results as well as severe disturbance of the granular bed. We also discuss results from several experiments designed to test the validity of various sampling protocols by varying parameters such as sampling location and frequency of sampling. These experiments illustrate the importance of effective sampling procedures to achieve the best and most efficient results.

Numerical characterization of low Reynolds number flow in the Kenics static mixer

Low Reynolds number flow in a six element Kenics static mixer was modeled using finite element computations. The numerical approach takes into account aspects of the fluid flow within the Kenics mixer which have been neglected in previous studies, including transitions between mixer elements and finite-thickness mixer plates. The pressure drop information obtained from the simulations was compared to several experimental correlations available in the literature for Kenics mixer pressure drop. Analysis of the low Reynolds number velocity field indicates a spatially periodic flow which matches the periodicity of the mixer geometry. Flow transitions at the entrance and exit of each element strongly affect the velocity field for up to ∼25% of the element’s length under creeping flow conditions. Comparison of the velocity field over a range of Reynolds numbers from 0.15 to 100 indicated that Reindependent velocity profiles are obtained up to Re=10, with significant deviations in the velocity field at Reynolds numbers above this limit. The magnitude of the rate-of-strain tensor, which represents an upper bound for mixing efficiency, was computed and profiled within the mixer. The profile for the magnitude of the rate-of-strain tensor was roughly uniform over the central 75% of a single mixer element, but shifted toward higher values in the end regions, indicating that the greatest potential mixing effects take place at the element-to-element transitions.