Numerical study on the effect of particle shape on mixers

Homogenization of particulate systems is a critical part in the processing of particulate materials to achieve consistency and ensure product quality. Homogenization is achieved by mixing, the aim is to obtain a final mixture that is homogeneous when mixing individual particulate constituents, in the sense of a uniform spatial mass distribution. Although there is always some measure of heterogeneity in a mixture this can be quantified by Gys sampling theory. This is critical for pharmaceutical industries in which it is essential that the variance of the active ingredients between tablets are within specified bounds. Although there have been numerous numerical studies on mixing using the Discrete Element Method (DEM), most studies to date have incorporated significant simplifications to reduce the computational time such as using mono-disperse size distributions, scaling up of particle size and spherical estimations of shape. The development of GPU based DEM simulations in the past few years significantly increased the number of spherical particles however most often at the expense of simplifying the physical interaction between particles. This oversimplification of particle shape has much wider primary implications as primary contact mechanisms such as angularity and locking are omitted. This is important in the pharmaceutical industry where the feed powders are often made from crystalline solids in which the shape of the individual particles are polyhedral. As this study demonstrates, this is significant in that the underlining dynamics of polyhedral particles is vastly different to that of spherical particles, resulting in tighter packing fractions different flow patterns, and percolation. In this paper we use the GPU based DEM code BlazeDEM3D-GPU to study and quantify the effect of particle shape in a high shear blade mixer

At-line validation of optical coherence tomography as in-line/at-line coating thickness measurement method

Optical Coherence Tomography (OCT) is a promising technology for monitoring of pharmaceutical coating processes. However, the pharmaceutical development and manufacturing require a periodic validation of the sensor's accuracy. For this purpose, we propose polyethylene terephthalate (PET) films as a model system, to periodically validate the measurements during manufacturing. This study proposes a new approach addressing the method validation requirement in the pharmaceutical industry and presents results for complementary methods. The methods investigated include direct measurement of the layer thickness using a micrometer gauge as reference, X-ray micro computed tomography, transmission and reflectance terahertz pulsed imaging, as well as 1D- and 3D-OCT. To quantify the significance of OCT for pharmaceutical coatings, we compared the OCT results for commercial Thrombo ASS and Pantoloc tablets with direct measurements of coating thickness via light microscopy of microtome cuts. The results of both methods correlate very well, indicating high intra- and inter-tablet variations in the coating thickness for the commercial tablets. The light microscopy average measured coating thickness of Thrombo ASS (Pantoloc) was 71.0 µm (83.7 µm), with an inter-coating variability of 8.7 µm (6.5 µm) and an intra-coating variability of 2.3 µm to 9.4 µm (2.1 µm to 6.7 µm)

Predicting capsule fill weight from in-situ powder density measurements using terahertz reflection technology

The manufacturing of the majority of solid oral dosage forms is based on the densification of powder. A good understanding of the powder behavior is therefore essential to assure high quality drug products. This is particularly relevant for the capsule filling process, where the powder bulk density plays an important role in controlling the fill weight and weight variability of the final product. In this study we present a novel approach to quantitatively measure bulk density variations in a rotating container by means of terahertz reflection technology. The terahertz reflection probe was used to measure the powder density using an experimental setup that mimics a lab-scale capsule filling machine including a static sampling tool. Three different grades of α-lactose monohydrate excipients specially designed for inhalation application were systematically investigated at five compression stages. Relative densities predicted from terahertz reflection measurements were correlated to off-line weight measurements of the collected filled capsules. The predictions and the measured weights of the powder in the capsules were in excellent agreement, where the relative density measurements of Lactohale 200 showed the strongest correlation with the respective fill weight (R 2 =0.995). We also studied how the density uniformity of the powder bed was impacted by the dosing process and the subsequent filling of the holes (with excipient powder), which were introduced in the powder bed after the dosing step. Even though the holes seemed to be filled with new powder (by visual inspection), the relative density in these specific segments were found to clearly differ from the undisturbed powder bed state prior to dosing. The results demonstrate that it is feasible to analyze powder density variations in a rotating container by means of terahertz reflection measurements and to predict the fill weight of collected capsules

Designing attractive models via automated identification of chaotic and oscillatory dynamical regimes

Chaos and oscillations continue to capture the interest of both the scientific and public domains. Yet despite the importance of these qualitative features, most attempts at constructing mathematical models of such phenomena have taken an indirect, quantitative approach, for example, by fitting models to a finite number of data points. Here we develop a qualitative inference framework that allows us to both reverse-engineer and design systems exhibiting these and other dynamical behaviours by directly specifying the desired characteristics of the underlying dynamical attractor. This change in perspective from quantitative to qualitative dynamics, provides fundamental and new insights into the properties of dynamical systems

Enantioselective Hydrogenations with Chiral Titanocenes

In this review article chiral titanocenes and their application for the enantioselective hydrogenations of different unsaturated compounds are discussed, with a special emphasis on the kinetics and the practicality of the developed systems. The nature of enantioselectivity and the hydrogenation mechanisms are reviewed as well. Catalyst immobilization and the different immobilization techniques are examined

Enantioselective Hydrogenations with Chiral Titanocenes

In this review article chiral titanocenes and their application for the enantioselective hydrogenations of different unsaturated compounds are discussed, with a special emphasis on the kinetics and the practicality of the developed systems. The nature of enantioselectivity and the hydrogenation mechanisms are reviewed as well. Catalyst immobilization and the different immobilization techniques are examined

Simulation Studies for the Effects of Particle Size and Blade Rake Angle on Particle Mixing

Solid particle mixing is an important unit operation in process industry. [...

Development of Micropellets for Buccal Drug Delivery

Introduction: Pellets are an attractive dosage form in the gender specific and pediatric therapy, since they offer the possibility of patient adapted dosing. [...

Simulation of Fluid Mixing and Dissolution Processes

Fluid mixing and dissolution processes are still an area of ongoing research. Numerical simulations have proven to be a valuable tool in understanding and optimizing industrial mixing problems [1]. [...