Robustness Testing of a Tablet Formulation Using Multivariate Design

ABSTRACT

A total of 45 experiments were carried out to evaluate the robustness of two similar tablet formulations—a product of two strengths—with respect to normal batch-to-batch variation of the excipients and the active pharmaceutical ingredient. The formulations consist of 10 ingredients. Because of the differing amounts of active pharmaceutical ingredients, the two formulations also differ in the amounts of two of the diluents and one of the binders. The excipients and active pharmaceutical ingredient were characterized in terms of multiple variables, and principal properties were calculated with principal component analysis. A Plackett and Burman design was applied to the principal properties. The relationships between the design factors and two responses, mean disintegration time and mean crushing strength, were evaluated by using regression methods. Both formulations were found to be robust under controlled conditions.     

Modeling and Flow Sheet Simulation of Selected Mechanical Recycling Processes for Li-Ion Batteries

To investigate the mechanical processes of Li-ion battery recycling in more detail, models for the different unit processes are to be developed. Here, model approaches for the cutting mill and the zig-zag-sifter are presented. These models are to be used in dynamic flow sheet simulations, with which the individual unit processes as well as the combination to a small process chain were simulated. Thereby, the dynamic interactions between the process steps were investigated, which can be used later for optimization and regulation of the processes. The particle sizes after the cutting mill process as well as the mass flow between the processes influence the separation behavior of the sifter. These changes in the separation function due to an increasing mass flow out of the mill are shown.     

A comparative performance study of common and popular task‐centric programming frameworks

Programmers today face a bewildering array of parallel programming models and tools, making it difficult to choose an appropriate one for each application. An increasingly popular programming model supporting structured parallel programming patterns in a portable and composable manner is the task‐centric programming model. In this study, we compare several popular task‐centric programming frameworks, including Cilk Plus, Threading Building Blocks, and various implementations of OpenMP 3.0. We have analyzed their performance on the Barcelona OpenMP Tasking Suite benchmark suite both on a 48‐core AMD Opteron 6172 server and a 64‐core TILEPro64 embedded many‐core processor. Our results show that the OpenMP offers the highest flexibility for programmers, and this flexibility comes to a cost. Frameworks supporting only a specific and more restrictive model, such as Cilk Plus and Threading Building Blocks, are generally more efficient both in terms of performance and energy consumption. However, Intel's implementation of OpenMP tasks performs the best and closest to the specialized run‐time systems. Copyright © 2013 John Wiley & Sons, Ltd.     

Wobbling in modern motorcycles

Serious personal injuries have been reported, caused by motorcycles which suddenly began to wobble when ridden at moderate to high speed. A random sample of 1043 owners of 1978–1982 model year motorcycles was interviewed concerning their experience of wobbling in 1982. The response rate was 95%. Wobbling was reported by 45% of the owners, 8% reported at least one incident of severe wobbling. This figure indicates that about 6000 riders in Sweden experienced severe wobbling during 1982. Wobbling increased proportionately both with the distance ridden and engine displacement and was highest among those riders who make heavy use of the engine's power. A statistically significant difference in wobbling was found between Japanese and other manufacturers. The reported average speed where wobbling occurred was 118 .     

Experimental assessment of grinding bead velocity distributions and stressing conditions in stirred media mills

Fine grinding in stirred media mills is an important process in mineral, chemical and pharmaceutical industry. The stressing mechanism in these mills is grinding through compression and shearing by grinding beads. A few studies have examined grinding bead transport in stirred media mills. Radiometric methods detect the local filling degree, but little is known about the experimental motion of the grinding beads in the mill. This study aims to investigate the position, velocity and radial circulation of individual grinding beads at different operation parameters (viscosity and tip speed) by a fast and inexpensive measurement technique. Additional information about stresses in the mill were derived, such as a relation between axial grinding media distribution and grinding bead velocity. As a result, the two investigated operation parameter (viscosity and tip speed) effect the grinding bead velocity and grinding bead transport in the mill. The mentioned results can be used to validate DEM simulation results.     

Multivariate methods in the development of a new tablet formulation: excipient mixtures and principal properties

A tablet formulation for direct compression has previously been studied using multivariate design. An optimization study of one of the most important tablet properties, disintegration time, revealed that excipients with Principal Properties (PP's) that were predicted as suitable by the model were not represented within the studied material. The feasibility of using mixtures of excipients in the multivariate approach to tablet formulation to solve this problem has been investigated in the present study. By mixing different excipients of the same excipient class, it should be possible to obtain mixtures with the predicted PP's, which in turn should give a formulation with the desired properties. In order to investigate the utility of this approach, separate mixture designs were applied to both binders and fillers (diluents). As reported here, the Partial Least Squares Projections to Latent Structures (PLS) model developed in the previously published screening study has been validated in the sense that the interesting region of the PP space identified in it has been shown to contain excipients, pure or mixed, that give the formulation suitable properties. Formulations with suitable properties were found with the mixture experiments. The local models also offer several alternatives for the composition of the formulation that yield the desired disintegration time.     

Flowability measurements of pharmaceutical powder mixtures with poor flow using five different techniques

Four different tablet formulations for direct compression with poor flow properties were tested regarding flowability using five different techniques: Hausner ratio, avalanching behavior, powder rheometer, uniaxial tester, and Jenike tester. In addition, the behavior of three of the formulations during emptying of the mixer and tableting was observed and compared to the results of the flowability measurements. The rank order correlation of the formulations was generally the same with all techniques. The flow properties measured by the different techniques reflected the behavior during processing of the powder mixtures.     

Boosting the performance of shared memory multiprocessors

Proposed hardware optimizations to CC-NUMA machines-shared memory multiprocessors that use cache consistency protocols-can shorten the time processors lose because of cache misses and invalidations. The authors look at cost-performance trade-offs for each