Recent advances in positron emission particle tracking: a comparative review.

Positron emission particle tracking (PEPT) is a technique which allows the high-resolution, three-dimensional imaging of particulate and multiphase systems, including systems which are large, dense, and/or optically opaque, and thus difficult to study using other methodologies. In this work, we bring together researchers from the world's foremost PEPT facilities not only to give a balanced and detailed overview and review of the technique but, for the first time, provide a rigorous, direct, quantitative assessment of the relative strengths and weaknesses of all contemporary PEPT methodologies. We provide detailed explanations of the methodologies explored, including also interactive code examples allowing the reader to actively explore, edit and apply the algorithms discussed. The suite of benchmarking tests performed and described within the document is made available in an open-source repository for future researchers.

Positron Emission Particle Tracking of Granular Flows.

Positron emission particle tracking (PEPT) is a noninvasive technique capable of imaging the three-dimensional dynamics of a wide variety of powders, particles, grains, and/or fluids. The PEPT technique can track the motion of particles with high temporal and spatial resolution and can be used to study various phenomena in systems spanning a broad range of scales, geometries, and physical states. We provide an introduction to the PEPT technique, an overview of its fundamental principles and operation, and a brief review of its application to a diverse range of scientific and industrial systems.

Roller compaction of moist pharmaceutical powders.

The compression behaviour of powders during roller compaction is dominated by a number of factors, such as process conditions (roll speed, roll gap, feeding mechanisms and feeding speed) and powder properties (particle size, shape, moisture content). The moisture content affects the powder properties, such as the flowability and cohesion, but it is not clear how the moisture content will influence the powder compression behaviour during roller compaction. In this study, the effect of moisture contents on roller compaction behaviour of microcrystalline cellulose (MCC, Avicel PH102) was investigated experimentally. MCC samples of different moisture contents were prepared by mixing as-received MCC powder with different amount of water that was sprayed onto the powder bed being agitated in a rotary mixer. The flowability of these samples were evaluated in terms of the poured angle of repose and flow functions. The moist powders were then compacted using the instrumented roller compactor developed at the University of Birmingham. The flow and compression behaviour during roller compaction and the properties of produced ribbons were examined. It has been found that, as the moisture content increases, the flowability of moist MCC powders decreases and the powder becomes more cohesive. As a consequence of non-uniform flow of powder into the compaction zone induced by the friction between powder and side cheek plates, all produced ribbons have a higher density in the middle and lower densities at the edges. For the ribbons made of powders with high moisture contents, different hydration states across the ribbon width were also identified from SEM images. Moreover, it was interesting to find that these ribbons were split into two halves. This is attributed to the reduction in the mechanical strength of moist powder compacts with high moisture contents produced at high compression pressures.

The effect of lubrication on density distributions of roller compacted ribbons.

Roller compaction is a continuous dry granulation process for producing free flowing granules in order to increase the bulk density and uniformity of pharmaceutical formulations. It is a complicated process due to the diversity of powder blends and processing parameters involved. The properties of the produced ribbon are dominated by a number of factors, such as the powder properties, friction, roll speed, roll gap, feeding mechanisms and feeding speed, which consequently determine the properties of the granules (size distribution, density and flow behaviour). It is hence important to understand the influence of these factors on the ribbon properties. In this study, an instrumented roller press developed at the University of Birmingham is used to investigate the effect of lubrication on the density distribution of the ribbons. Three different cases are considered: (1) no lubrication, (2) lubricated press, in which the side cheek plates of the roller press are lubricated, and (3) lubricated powder, for which a lubricant is mixed into the powder. In addition, how the powders are fed into the entry region of the roller press and its influence on ribbon properties are also investigated. It is found that the method of feeding the powder into the roller press plays a crucial role in determining the homogeneity of the ribbon density. For the roller press used in this study, a drag angle (i.e., the angle formed when the powder is dragged into the roller press) is introduced to characterise the powder flow pattern in the feeding hopper. It is shown that a sharper drag angle results in a more heterogeneous ribbon. In addition, the average ribbon density depends upon the peak pressure and nip angle. The higher the peak pressure and nip angle are, the higher the average ribbon density is. Furthermore, the densification behaviour of the powder during roller compaction is compared to that during die compaction. It has been shown that the densification behaviour during these two processes is similar if the ribbons and the tablets have the same thickness.

The effects of high shear blending on alpha-lactose monohydrate.

alpha-Lactose monohydrate is an important pharmaceutical excipient used extensively in dry powder inhaler (DPI) formulations. The ways in which a high shear blending process affect this material have been investigated and important process parameters have been identified. Total energy input (kJ/kg), blade design and the conditions in which lactose was stored prior to blending were found to have the most significant effect on the apparent particle size distribution of the processed material, which may subsequently affect the performance of DPI formulations. The power conditions used during blending, equipment temperature and humidity of the headspace above the powder were found to be less important in this respect. Additionally, it was found that high energy blending could induce changes in the water sorption characteristics of the material, although the formation of amorphous material could not be confirmed.

The relation between granule size, granule stickiness, and torque in the high-shear granulation process.

PURPOSE: To investigate the background of the observed relationship between measured torque and granule size in high-shear granulation processes. METHODS: Torque was measured during the granulation process; the behavior of individual wet granules during compaction was investigated using micromanipulation. Surface properties of wet granules were manipulated by coating them with talc. RESULTS: The torque-granule size relationship could not be explained by the rise in mass of the individual granules; it occurs rather through an increase in stickiness of the granules when the moisture content is increased. Obviously, the increased stickiness that causes the granules to grow also increases the torque. Increased stickiness was shown to be the result of an increased deformability of the granules at higher moisture contents, in combination with a change in surface properties. The elastic-plastic behavior (ratio of elastic to plastic deformation) was found to change at increasing moisture contents. CONCLUSIONS: Our results imply that changes in the stickiness of the granular material that may be caused by changes in composition shift the torque-size relationship. This may be of particular importance when, for example, granulation results from placebo batches are used to predict the granule size of drug-containing batches.

The effect of the amount of binder liquid on the granulation mechanisms and structure of microcrystalline cellulose granules prepared by high shear granulation.

The structure of granules changes during the high shear granulation process. The purpose of this research was to investigate the effect of the amount of binder liquid on the structure of the granules and the structural changes which occur during the granulation process, using microcrystalline cellulose (MCC) and water as the model system. The structure is the result of the granulation mechanism; therefore, conclusions can be drawn about the latter by studying the former. X-ray microtomography and scanning electron microscopy (SEM) were applied in order to visualise the densification process of granules, which were first freeze dried in order to preserve their structure. Variations in their porosity were quantified by applying image analysis to the tomography results. In order to link the granule mechanical properties to their structural differences, a micromanipulation technique was used to measure granule resistance to deformation. MCC granules granulated with 100% (w/w) water showed increased densification with time, as expected; detailed examination showed that densification is more pronounced in the core of the granule; whereas the outer part remained more porous. Increased densification reduces deformability, so that granules become more resistant to breakage. The lower deformability of the densified granules in the final stages of granulation might result in establishment of equilibrium between attrition and growth, without substantial gross breakage. On the other hand, when more water was used (125%, w/w), densification was hardly observed; the porosity of the granule core was still high even after prolonged granulation times. This may be explained by the fact that higher water content increases the ease of deformation of granules. This increased deformability led to significant granule breakage even during the final phases of the granulation process. Therefore, for these granules a final equilibrium between breakage and coalescence might be established. This also explains why more granules produced with 125% granulation liquid were composed of fragments of irregular shape. Our results establish the link between the granulation behaviour of MCC in the latter stages and the material structure of these granules, which is determined by their liquid content. The process conditions (amount of liquid) to be chosen depend largely on the final purpose for which the granular material is produced.