In roller compaction, particle distribution is recognised as a critical parameter affecting downstream process performance and product quality.
A roller compaction process is designed to yield consistent downstream tablet compression, resulting in uniform dissolution and content uniformity. A successful roller compaction process should produce a granule with consistent particle size distribution, density and porosity control.
Inconsistencies can occur during granulation scale-up however, due to a change in raw materials or process dynamics.
Working in collaboration with Patheon, Mettler Toledo now have a way to optimse the roller compaction process using their FBRM particle characterisation technology at-line to map the design space and optimise a series of roller compaction runs, all while varying vertical/horizontal feed speed, roller compaction force, and mill speed.
Characterising particle distribution allows users to directly link process control parameters to product quality. By designing a robust process, consistent processing from dry granulation to tablet compression can be achieved.
FBRM particle characterisation technology is typically inserted in-line in a collection funnel downstream of the Comil and powder flows over the probe tip. This provides a representative measurement due to measuring in-line or at-line within concentrated particle systems, increasing sample size and providing high sensitivity to fine particles.
In a recent 19-batch DoE, performed to help understand processing parameters affecting downstream product quality, FBRM particle characterisation technology was used to measure and control changes in particle count and dimension. In this case, an at-line method was used to sample 10g of powder downstream and dispersed in 100g of mineral oil.
Results showed that high roller compaction force and mill speed resulted in coarser particles with lower porosity and density, whereas low compaction force and mill speed corresponded to a higher level of fine particles, porosity and density.
In general, roller compaction force significantly affected ribbon density, porosity compacts and milled compact particle size. By measuring granule dimensions in real time, roller compaction process conditions can be controlled to target specific mean dimensions. Since mean dimensions correlate to granule porosity, there is an opportunity for real-time control ensuring consistency.
Roller compaction is a complex process with competing mechanisms of breakage and agglomeration. By using Mettler Toledo's FBRM particle characterisation technology, it is now possible to quantify the effect of critical process parameters and correlate this to ribbon parameters.
By characterising these effects, it is possible to reduce scale-up time, minimise upsets and troubleshoot issues.
Inline particle characterisation is also used to identify screen breaks and hardware malfunctions to help reduce manufacturing costs.