Benjamin J. Glasser

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.

Impact of drying on the catalyst profile in supported impregnation catalysts

Abstract The impact of drying conditions and system properties on the final catalyst profile in supported impregnation catalysts is studied. A model is developed, which accounts for convective flow in the liquid phase, multi-component diffusion of the metal in the liquid phase, metal adsorption on the porous support, and heat transport. Transport of the gas and liquid phase are described by the dusty gas model and Darcys law, respectively. Transport of charged particles (dissolved metal and its ion counterpart) in the liquid solution, i.e., the convective and diffusive ion transport, are modeled by the Nernst–Plank equation. Metal adsorption on the porous support is modeled by a Langmuir adsorption isotherm. It was shown that in the case of strong adsorption, drying does not affect the final metal profile. In such cases, the profile is mainly determined during impregnation. In the case of weak metal adsorption, drying strongly impacts the final catalyst distribution. Accumulation of the metal at the external particle surface (egg-shell profile) becomes significant with increasing drying rate, since convective flow towards the surface is the dominant transport mechanism. Egg-shell catalysts are also obtained, if the permeability of the support is very high, or if the liquid solution has low viscosity. If metal back-diffusion is strong, the metal is transported towards the particle center, leading to uniform or decreasing egg-yolk catalysts. A dimensional analysis of the model equations showed that the final catalyst profile is determined by three dimensionless groups, which describe the relative strength of convection, diffusion, and adsorption. Maps were computed that show regions of different catalyst profiles. Therefore, knowledge of these three dimensionless groups allows the prediction of the final catalyst profile.

Scale dependence, correlations, and fluctuations of stresses in rapid granular flows

It is shown that, unlike in simple molecular fluids, the stress field in granular fluids may be strongly scale, or resolution, dependent. This is a result of the intrinsic lack of scale separation in these fluids. Another consequence of the lack of scale separation in granular fluids is that microscopic stress fluctuations, whose origin (like in molecular fluids) is the underlying discreteness of the system, may appear as observables in macroscopic measurements; the correlation (or decay) time of the stress fluctuations is of the order of the mean-free time, which is also a macroscopic time. All of these properties are intrinsic to granular fluids and not (for example) results of the practical lack of scale separation that is dictated by the fact that grains are of macroscopic dimensions or the limited statistics in simulations. Numerical evidence, based on molecular-dynamic simulations of shear flows of smooth disks in a two-dimensional enclosure, serves to demonstrate the above phenomena.

Batch Uptake of Lysozyme: Effect of Solution Viscosity and Mass Transfer on Adsorption

In this study, solid‐phase adsorption by macroporous and hyper‐diffusive resins was investigated in a batch uptake adsorption system to quantify solid‐phase diffusion rates as a function of bulk phase viscosity. The performance of chromatographic resins used for adsorption of proteins is dependent on several factors including solid and liquid‐phase diffusivity, boundary layer mass transfer, and intraparticle mass transfer effects. Understanding these effects is critical to process development and optimization of both packed and fluidized bed adsorption systems. The macroporous resin used here was Streamline SP, and the hyper‐diffusive resin was S‐HyperD LS. Both have been frequently used in fluidized bed adsorption of proteins; however, factors that affect uptake rates of these media are not well quantified. Adsorption isotherms were well represented by an empirical fit of a Langmuir isotherm. Solid‐phase diffusion coefficients obtained from simulations were in agreement with other models for macroporous and hyper‐diffusive particles. S‐HyperD LS in the buffer system had the highest uptake rate, but increased bulk phase viscosity decreased the rate by approximately 50%. Increases in bulk phase viscosity increased film mass transfer effects, and uptake was observed to be a strong function of the film mass transfer coefficient. Uptake by Streamline SP particles was slower than S‐HyperD in buffer, due to a greater degree of intraparticle mass transfer resistance. The effect of increased film mass transfer resistance coupled with intraparticle mass transfer resistances at an increased bulk phase viscosity resulted in a decrease of 80% in the uptake rate by Streamline SP relative to S‐HyperD.

Impact of agitated drying on crystal morphology: KCl–water system

Abstract An experimental procedure was developed to study agitated drying of crystals. The procedure quantifies the impact of drying conditions (temperature, agitation speed and vacuum) on crystal properties (size and shape distribution). KCl was used as a model compound. The morphology of the crystals was determined using light microscopy and image analysis. The analysis of the transient behavior of the crystal size distribution showed that there is a permanent competition between attrition and agglomeration during drying. However, these two phenomena only had a significant effect on the crystal size distribution when the moisture content was below a critical value. In particular, it was found that attrition dominates the drying process when the drying rate is low and/or the shear rate is high. Under these conditions, the drying time is long enough for particles to encounter many particle-impeller and particle–particle collisions that can produce small crystal fragments. For higher drying rates, which are obtained at high temperature and low pressure, the number of ‘collisions’ decreases, stronger agglomerates are formed and thus agglomeration becomes more dominant. Other physical phenomena, which can take place during drying, such as crystal redissolution, had no significant impact on crystal morphology.

Producing Transportation Fuels with Less Work

New reaction chemistry may reduce the energy input and carbon dioxide emissions from processes that convert coal into liquid fuels.

A Taylor vortex analogy in granular flows

Fluids sheared between concentric rotating cylinders undergo a series of three-dimensional instabilities. Since Taylors archetypal 1923 study, these have proved pivotal to understanding how fluid flows become unstable and eventually undergo transitions to chaotic or turbulent states. In contrast, predicting the dynamics of granular systems—from nano-sized particles to debris flows—is far less reliable. Under shear these materials resemble fluids, but solid-like responses, non-equilibrium structures and segregation patterns develop unexpectedly. As a result, the analysis of geophysical events and the performance of largely empirical particle technologies might suffer. Here, using gas fluidization to overcome jamming, we show experimentally that granular materials develop vortices consistent with the primary Taylor instability in fluids. However, the vortices observed in our fluidized granular bed are unlike those in fluids in that they are accompanied by novel mixing–segregation transitions. The vortices seem to alleviate increased strain by spawning new vortices, directly modifying the scale of kinetic interactions. Our observations provide insights into the mechanisms of shear transmission by particles and their consequent convective mixing.

Shear instabilities in granular flows

Unstable waves have been long studied in fluid shear layers. These waves affect transport in the atmosphere and oceans, in addition to slipstream stability behind ships, aeroplanes and heat-transfer devices. Corresponding instabilities in granular flows have not been previously documented, despite the importance of these flows in geophysical and industrial systems. Here we report that breaking waves can form at the interface between two streams of identical grains flowing on an inclined plane downstream of a splitter plate. Changes in either the shear rate or the angle of incline cause such waves to appear abruptly. We analyse a granular flow model that agrees qualitatively with our experimental data; the model suggests that the waves result from competition between shear and extensional strains in the flowing granular bed. We propose a dimensionless shear number that governs the transition between steady and wavy flows.

Hydrodynamics of a uniform liquid-fluidized bed containing a binary mixture of particles

Abstract This paper examines the steady state hydrodynamics of a fluidized bed of two particle species, having different diameters and densities. Steady state mixing solutions of the volume-averaged equations of motion for the fluid and particles are sought. An expression for the fluid–particle interactive force (in the mixture) is postulated to close the continuum equations of motion using an excluded volume assumption. Solutions to the equations are found for a fluidized bed of glass beads and carbon char in water. It is shown that the solution sets not only characterize the composition and expansion behavior of the mixing states, but also provide a description of the observed phenomenon of “layer inversion”. The model identifies three possible layer inversion scenarios, one of which has been observed experimentally. Comparison with experimental data suggest that the hydrodynamic mechanism of fluid–particle interaction is not fully captured with an excluded volume assumption. Thus, we show how experimental data can be used to derive functional forms for expressing the complex hydrodynamic behavior within the framework of the model.

Monitoring Blending of Pharmaceutical Powders with Multipoint NIR Spectroscopy

Blending of powders is a crucial step in the production of pharmaceutical solid dosage forms. The active pharmaceutical ingredient (API) is often a powder that is blended with other powders (excipients) in order to produce tablets. The blending efficiency is influenced by several external factors, such as the desired degree of homogeneity and the required blending time, which mainly depend on the properties of the blended materials and on the geometry of the blender. This experimental study investigates the mixing behavior of acetyl salicylic acid as an API and α-lactose monohydrate as an excipient for different filling orders and filling levels in a blender. A multiple near-infrared probe setup on a laboratory-scale blender is used to observe the powder composition quasi-simultaneously and in-line in up to six different positions of the blender. Partial least squares regression modeling was used for a quantitative analysis of the powder compositions in the different measurement positions. The end point for the investigated mixtures and measurement positions was determined via moving block standard deviation. Observing blending in different positions helped to detect good and poor mixing positions inside the blender that are affected by convective and diffusive mixing.