Application of feeding guiders to improve the powder distribution in the two scales of roller compactors.

Roller compaction is a continuous dry granulation process, where the powder is compressed between two counter-rotating rollers and compacted into ribbons. The quality and homogeneity of the granulate is determined by the uniformity and porosity of the ribbon, which depends on the feeding process of the primary powder to the rollers, the flow properties of the primary powder and process parameters such as roller forces. Previous work was conducted to improve the powder flow and distribution in the feeding zone by developing new feeding guiders, which are located in the feeding zone close to the rollers on the lab-scale roller compactor Alexanderwerk WP120 Pharma (Yu et al., 2018). These new feeding guiders were used to reduce the amount of powder that is delivered to the centre of the rollers and increase the amount of powder that is delivered to the sides of the rollers, in comparison to the original feeding guiders. This modified concept using new feeding guiders has been applied to the large-scale roller compactor Alexanderwerk WP200 Pharma in the present work. In order to evaluate the homogeneity of the ribbon properties across the ribbon width, the temperature profile and porosity distribution across the ribbon width were measured. The new feeding guiders resulted in ribbons being produced with a more uniform temperature profile and porosity distribution across the ribbon width when using the small and large scale roller compactors at different process parameters.

Roller compaction: Ribbon splitting and sticking.

Roller compaction is the main technique employed in dry granulation. Ribbon sticking and splitting are among the major factors that can hinder the use of this process for some formulations. Ribbon splitting can occur either transversally (through the ribbon thickness) or longitudinally (through the ribbon width). It was observed that transverse splitting is commonly associated with sticking of the split ribbons to the rollers and results in an inferior performance of the process. Longitudinal splitting is associated with an across-width distribution of the ribbon density so that there may an adverse effect on the mechanical strength and dissolution properties of the tablets formed from the milled granules. The aim of the current work was to elucidate the mechanisms of splitting by an experimental study involving single component powders with a range of yield strengths, including those that are commonly used as excipients. Both smooth and knurled rollers were employed without and with lubrication by applying magnesium stearate to the rollers. The minimum gap was fixed and the maximum roll stress was varied. The observed trends for the smooth rollers were rationalised in terms of a splitting index, which is a measure of the residual stresses driving crack growth relative to the tensile strength of the ribbons. There was a lower limit at which splitting was observed but the occurrence of transverse splitting decreased and that for longitudinal splitting increased with increasing values of the index, which was accompanied by an increase in mixed transverse-longitudinal splitting. Transverse splitting was always associated with sticking to the rollers and was prevented by external lubrication. The main difference with the knurled rollers was that in some cases transverse splitting occurred without sticking to the rollers. A detailed discussion of the mechanisms involved is presented.

Assessing Particle Segregation Using Near-Infrared Chemical Imaging in Twin Screw Granulation.

In the present study the application of near-infrared chemical imaging (NIR-CI) for assessing particle segregation in granules from continuous twin screw granulation (TSG) granules, were the complex attributes of the machinery configuration in relation to particle segregation is not well understood was investigated. Experiments were performed along the compartmental length of the TSG barrel channel by varying the screw element type and liquid binder viscosity. Examination of the data showed a direct correlation between dispersion due to shear force and de-mixing of particles, which allowed for identification of fundamental granule segregation mechanisms affecting content uniformity in TSG. Particle segregation behavior was linked to dispersion due to shear force through a proposed regime mapping approach which links de-mixing potential to controlling granule formation mechanisms with a new dimensionless mixing number. This was carried out in order to provide a general guideline of how particles segregate along the length of the TSG barrel channel.

Implementation of an online thermal imaging to study the effect of process parameters of roller compactor.

During roller compaction, not only the properties of the primary powder affect the product quality but also the process parameters. Any change in the process parameters during roller compaction will result in changing the properties of the ribbon. In this study, the temperature of the ribbon during production was monitored online using a thermal camera. The information from the thermal camera was used to explain the differences in ribbon properties at varying process parameters. Lactose powder was used as a primary powder, and ribbons were produced at different process parameters. The surface temperature of the ribbon during production was found to increase with increasing both the gap between the two rollers and the roller speed. This was attributed to the screw feeder speed, which increased to feed additional powder as required to adjust to the change in process parameters. Increasing the roller gap resulted in wider ribbons and decreased the percentage of fines in the product, which was a signature of better powder distribution across the roller width. The results were also supported by the uniform temperature distribution recorded across the ribbon width. It was found that increasing the roller speed during roller compaction decreased the width of the ribbon while increasing the percentage of fines in the product. The feeder screw speed was found to have a similar effect as the roller gap.

Roller compaction: Effect of relative humidity of lactose powder.

The effect of storage at different relative humidity conditions, for various types of lactose, on roller compaction behaviour was investigated. Three types of lactose were used in this study: anhydrous lactose (SuperTab21AN), spray dried lactose (SuperTab11SD) and α-lactose monohydrate 200M. These powders differ in their amorphous contents, due to different manufacturing processes. The powders were stored in a climatic chamber at different relative humidity values ranging from 10% to 80% RH. It was found that the roller compaction behaviour and ribbon properties were different for powders conditioned to different relative humidities. The amount of fines produced, which is undesirable in roller compaction, was found to be different at different relative humidity. The minimum amount of fines produced was found to be for powders conditioned at 20-40% RH. The maximum amount of fines was produced for powders conditioned at 80% RH. This was attributed to the decrease in powder flowability, as indicated by the flow function coefficient ffc and the angle of repose. Particle Image Velocimetry (PIV) was also applied to determine the velocity of primary particles during ribbon production, and it was found that the velocity of the powder during the roller compaction decreased with powders stored at high RH. This resulted in less powder being present in the compaction zone at the edges of the rollers, which resulted in ribbons with a smaller overall width. The relative humidity for the storage of powders has shown to have minimal effect on the ribbon tensile strength at low RH conditions (10-20%). The lowest tensile strength of ribbons produced from lactose 200M and SD was for powders conditioned at 80% RH, whereas, ribbons produced from lactose 21AN at the same condition of 80% RH showed the highest tensile strength. The storage RH range 20-40% was found to be an optimum condition for roll compacting three lactose powders, as it resulted in a minimum amount of fines in the product.

Roller compaction: Effect of morphology and amorphous content of lactose powder on product quality.

The effect of morphology and amorphous content, of three types of lactose, on the properties of ribbon produced using roller compaction was investigated. The three types of lactose powders were; anhydrous SuperTab21AN, α-lactose monohydrate 200 M, and spray dried lactose SuperTab11SD. The morphology of the primary particles was identified using scanning electron microscopy (SEM) and the powder amorphous content was quantified using NIR technique. SEM images showed that 21AN and SD are agglomerated type of lactose whereas the 200 M is a non-agglomerated type. During ribbon production, an online thermal imaging technique was used to monitor the surface temperature of the ribbon. It was found that the morphology and the amorphous content of lactose powders have significant effects on the roller compaction behaviour and on ribbon properties. The agglomerated types of lactose produced ribbon with higher surface temperature and tensile strength, larger fragment size, lower porosity and lesser fines percentages than the non-agglomerated type of lactose. The lactose powder with the highest amorphous content showed to result in a better binding ability between the primary particles. This type of lactose produced ribbons with the highest temperature and tensile strength, and the lowest porosity and amount of fines in the product. It also produced ribbon with more smooth surfaces in comparison to the other two types of lactose. It was noticed that there is a relationship between the surface temperature of the ribbon during production and the tensile strength of the ribbon; the higher the temperature of the ribbon during production the higher the tensile strength of the ribbon.