An evaluation carried out by Freeman Technology and Gerteis Maschinen+Processengineering AG illustrates the value of multivariate powder characterization for the optimization of dry granulation using roller compaction. Previous studies have shown how critical process parameters (CPPs) in wet granulation operations can be associated with critical quality attributes (CQAs) of a tablet . This additional work demonstrates how a roller compaction process also can be managed to control granule properties that are known to impact CQAs of the final product.
Granulation typically is used to combine fine particles into larger granules to reduce segregation, promote content uniformity and generally produce materials that are easier to handle. It often is employed in applications such as tabletting to improve operational efficiency and enhance final product quality.
Quality by Design (QbD) requires a detailed understanding of the relationship between materials and processes. Previous studies have shown how changes to CPPs in a granulation process can influence properties of resulting granulate as well as the final product, so it is essential that this relationship is fully understood .
The current study focused exclusively on roller compaction — a continuous process that uses an auger feed system (screw feeder) to deliver powder to a set of rollers that produce a dense, thin ribbon of material, typically consisting of sharp-edged particles. This material then can be milled to optimize particle size distribution prior to mixing with other materials into the final blend.
A fundamental requirement for moisture- or heat-sensitive materials, dry granulation is critical to many pharmaceutical, food and chemical manufacturing processes. A roller compactor is a relatively low-cost capital investment that can reliably convert fine, difficult-to-handle powders into granules with a high degree of density uniformity that flow more freely than their constituent materials.
The simple mechanism is robust and easy to maintain, which minimizes downtime, and also highly energy efficient. The combination of cost efficiency and reliable operation makes roller compaction a smart choice for lean manufacturing facilities.
Measuring Powder Flow
Optimization of powder processes relies on understanding the characteristics of materials and how they flow through the manufacturing equipment. Powder flowability is therefore a relevant parameter to inform equipment selection and maintain process performance.
Options for measuring powder flow range from simple, single-number traditional techniques to automated multivariate methods using sophisticated instrumentation. Cost efficiency demands that powder characterization techniques meet requirements without becoming overly complex. Test methods must:
1. Deliver results that are repeatable, reproducible and independent of the operator.
2. Reflect the actual process being evaluated (e.g., employ representative stress and flow regimes).
3. Provide sufficient sensitivity to detect subtle variations in powder characteristics that may be independent of physical particle properties yet still influence in-process performance.
Characterization of granules prior to tabletting, for example, should focus on properties relating to optimal tablet production and final tablet quality, and how changes in granulation parameters will affect these properties.
A Valuable Study
Freeman and Gerteis jointly investigated the dynamic flow, bulk and shear properties of a granulate produced via roller compaction to assess the impact of changing machine settings. Granules were produced using a model dry granulation blend in a Gerteis Mini-Pactor roller compaction unit. A Freeman Technology FT4 powder rheometer then characterized the resulting granules, to measure dynamic flow, bulk and shear properties in accordance with the standard test methodologies for the instrument .
In the compactor (Figure 1), the dry powder enters through an inlet funnel on the top of the unit. An agitator can be included to improve powder flow while a feed auger controls flow to the tamp auger. The tamp auger then delivers powder to the compaction zone, with additional input via a small hopper if necessary.
As the powder flows between the rollers, it experiences a closely monitored compacting force. The resulting ribbon of material then is passed through an integrated rotor or mill with a specific mesh size that defines an upper granule size, such that 90% of granules in any given volume are below the specified mesh size.
For any roller compactor, the applied compaction force and the distance between the rollers control the properties of resulting granules. Compaction force is defined as the compressive stress applied to the powder and is measured in kN/cm (force per cm roll width). At any given roller force, the thickness of the compacted ribbon directly correlates to the rate at which the powder is fed to the rollers. If the distance (in mm) between the rollers, i.e., the roll gap, is maintained at a fixed value, variation in feed materials will lead to variations in ribbon properties, performance of the granulate and, therefore, final product quality. To ensure consistency in applied compaction force and minimize fluctuations in the ribbon and granulated material, Gerteis machines employ a floating roll gap design to allow the distance between rollers to vary around a set point relative to the amount of powder being fed to them.