Modelling the effect of L/S ratio and granule moisture content on the compaction properties in continuous manufacturing.

The pharmaceutical field is currently moving towards continuous manufacturing pursuing reduced waste, consistency, and automation. During continuous manufacturing, it is important to understand how both operating conditions and material properties throughout the process affect the final properties of the product to optimise and control production. In this study of a continuous wet granulation line, the liquid to solid ratio (L/S) and drying times were varied to investigate the effect of the final granule moisture content and the liquid to solid ratio on the properties of the granules during tabletting and the final tensile strength of the tablets.

Influence of localized thermal effects on the reconstitution kinetics of lactose-coated whole milk powder.

Reconstitution of dairy powders is strongly influenced by the presence and physical state of fat on the particle surface. The present study investigates the effect of a micronized lactose coating on the physical state of the fat and the reconstitution kinetics of whole milk powder at four different temperatures (4/21/40/60 °C) and two stirring rates (400/800 rpm). For this purpose, two types of micronized lactose were used as coating materials: crystalline and amorphous.

Twin screw granulation: A simpler re-derivation of quantifying fill level.

The fill level is defined as the volume occupied by the powder and granules inside the twin-screw granulator in proportion to the maximum barrel channel void 'free' volume. In literature, the fill level is one of the key factors that determine the final granule properties as it relies on several factors such as the screw speed, screw element geometry, mass flow rate and barrel length. However, quantitative prediction of the fill level in twin-screw granulation (TSG) is still a developing area, which is required to enable effective development of process design space, to yield a product with desired quality attributes for all process scale levels (small to large equipment).

Roller compaction: Infrared thermography as a PAT for monitoring powder flow from feeding to compaction zone.

Roller compaction is a continuous dry granulation process, in which powder is compressed by two counter-rotating rollers. During this process, the powder feeding to the compaction zone has a significant effect on product quality. This work investigates the flow of powder from the feeding zone to the compaction zone using online infrared thermography as Process Analytical Technology (PAT) which is achieved via a specially built cheek plate (side-sealing).

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.

Wetting of binary powder mixtures.

The wetting process involved when a liquid droplet comes into contact with a mixture of particles is a complex phenomenon which is often understood by reference to Cassie-Baxter theory. However, various authors have applied the Cassie-Baxter theory for the prediction of contact angles on two-component mixtures without success. We hypothesise that the main difficulty in applying the Cassie-Baxter theory to mixtures is that if the particles differ in size, it is possible for the small particles to coat the large particles, so reducing the available surface area of the large particles.

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.

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).

Roller compaction: the effect of plastic deformation of primary particles with wide range of mechanical properties.

Understanding the compaction behaviour of the primary powder in the roller compaction process is necessary to be able to better control the quality of the product. In this study, the plastic deformation of the primary particles was evaluated by determining two mechanical properties: the nano-indentation hardness and the viscoelasticity of the primary powder. The nano-indentation hardness of eight different materials with a wide range of mechanical properties was determined by indenting the surface of the single primary particle, whereas the viscoelasticity was evaluated for a powder bed using the creep test.

Twin Screw Granulation: Effects of Properties of Primary Powders.

Lactose and mannitol are some of the most commonly used powders in the pharmaceutical industry. The limited research published so far highlights the effects of process and formulation parameters on the properties of the granules and the tablets produced using these two types of powders separately. However, the comparison of the performance of these two types of powders during twin screw wet granulation has received no attention.

Twin Screw Granulation: An Investigation of the Effect of Barrel Fill Level.

This paper focuses on investigating the influence of varying barrel fill levels on the mean residence time, granule properties (median size, size distribution, and shape), and tensile strength of tablets. Specific feed load (SFL) (powder feed rate divided by screw speed) and powder feed number (PFN) (i.e.

Improving feeding powder distribution to the compaction zone in the roller compaction.

In the roller compaction process, powder flow properties have a significant influence on the uniformity of the ribbon properties. The objective of this work was to improve the powder flow in the feeding zone by developing novel feeding guiders which are located in the feeding zone close to the rollers in the roller compactor (side sealing system). Three novel feeding guiders were designed by 3D printing and used in the roller compactor, aiming to control the amount of powder passing across the roller width.

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.

Transparent predictive modelling of the twin screw granulation process using a compensated interval type-2 fuzzy system.

In this research, a new systematic modelling framework which uses machine learning for describing the granulation process is presented. First, an interval type-2 fuzzy model is elicited in order to predict the properties of the granules produced by twin screw granulation (TSG) in the pharmaceutical industry. Second, a Gaussian mixture model (GMM) is integrated in the framework in order to characterize the error residuals emanating from the fuzzy model.

Investigating the effect of processing parameters on pharmaceutical tablet disintegration using a real-time particle imaging approach.

Tablet disintegration is a fundamental parameter that is tested in vitro before a product is released to the market, to give confidence that the tablet will break up in vivo and that active drug will be available for absorption. Variations in tablet properties cause variation in disintegration behaviour. While the standardised pharmacopeial disintegration test can show differences in the speed of disintegration of different tablets, it does not give any mechanistic information about the underlying cause of the difference.

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.

Twin screw wet granulation: Effect of process and formulation variables on powder caking during production.

This work focuses on monitoring the behaviour and the mass of the built up/caking of powder during wet granulation using Twin Screw Granulator (TSG). The variables changed during this work are; powder (α-lactose monohydrate and microcrystalline cellulose (MCC)), the screw configuration (conveying and kneading elements) and the weight percentage of hydroxypropyl-methyl cellulose (HPMC) dissolved in the granulation liquid (i.e.

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.

Roller compactor: The effect of mechanical properties of primary particles.

In this study, the nano-indentation hardness of a single primary particle was measured for six different materials; microcrystalline cellulose, hydroxypropyl methylcellulose, maltodextrin, lactose, sodium carbonate and calcium carbonate. This was linked to the properties of the ribbons produced by roller compactor at different hydraulic pressures in the range of 30-230 bar. The main investigated ribbon properties were strength, porosity and width.

Twin screw wet granulation: Binder delivery.

The effects of three ways of binder delivery into the twin screw granulator (TSG) on the residence time, torque, properties of granules (size, shape, strength) and binder distribution were studied. The binder distribution was visualised through the transparent barrel using high speed imaging as well as quantified using offline technique. Furthermore, the effect of binder delivery and the change of screw configuration (conveying elements only and conveying elements with kneading elements) on the surface velocity of granules across the screw channel were investigated using particle image velocimetry (PIV).

Granulation of increasingly hydrophobic formulations using a twin screw granulator.

The application of twin screw granulation in the pharmaceutical industry has generated increasing interest due to its suitability for continuous processing. However, an understanding of the impact of formulation properties such as hydrophobicity on intermediate and finished product quality has not yet been established. Hence, the current work investigated the granulation behaviour of three formulations containing increasing amounts of hydrophobic components using a Consigma™-1 twin screw granulator.

Twin screw granulation: steps in granule growth.

The present work focuses on the study of the progression of granules in different compartments along the length of screws in a twin screw granulator (TSG). The effects of varying powder feed rate; liquid to solid ratio and viscosity of granulation liquid on properties of granules was studied. The bigger granules produced at the start of the process were found to change in terms of size, shape and strength along the screw length at all the conditions investigated.

An investigation of the influence of process and formulation variables on mechanical properties of high shear granules using design of experiment.

Being able to predict the properties of granules from the knowledge of the process and formulation variables is what most industries are striving for. This research uses experimental design to investigate the effect of process variables and formulation variables on mechanical properties of pharmaceutical granules manufactured from a classical blend of lactose and starch using hydroxypropyl cellulose (HPC) as the binder. The process parameters investigated were granulation time and impeller speed whilst the formulation variables were starch-to-lactose ratio and HPC concentration.