Spatial filter techniques, along with delivering real-time particle size measurement, offer several further attractions such as simple hardware requirements, ease of use and reasonable commercial cost. It is possible to tailor the process interface used to the application enabling SFT to be used in the monitoring of all types of granulation equipment.
Probes using SFT measure in-line and can be directly inserted to a process vessel, granulator or line. They can reliably measure even in sticky damp environments with a standard measurement range spanning 50 to 6000 microns.
One can use inline dispersion systems for consistent presentation or dilute the process stream wherever needed, but these are integral to the probe. There are no moving parts in SFT probes and they are available in a range of lengths meaning that the technology such as laser diffraction easily transitions from development through to commercial production.
SFT is a chord length, number based sizing method used for collecting data for individual particles for developing a particle size distribution. It involves spatial filtering velocimetry and spot scanning. The sequential interruption of linearly neighboring fiber elements of the spatial filter detector help calculate particle velocity with each particle triggering a burst signal, the frequency of which is directly proportional to particle velocity. A secondary signal is used to determine particle size, the secondary signal being a measure of the length of time for which the particle blocks a single optical fiber.
Case Study: Using SFT for Tracking Fluid Bed Granulation
Batch or continuous mode is used to operate fluid bed granulation processes. Figure 1 shows the results of an experimental study of a batch fluidized bed granulation of 15 Kg of lactose/cellulose mixture, performed in a pilot scale granulator, a Glatt GPCG 15 with top spray configuration.
Figure 1. Particle size data based on chord length measurement (x10, x50 and x90).
A Parsum IPP70 SFT probe is used to measure particle size data in-line. The granulation liquid feed rate, temperature and flow rate of fluidization air were changed to target specific product quality goals relating to drying behavior, solubility and agglomerate formation by attaining a specific particle size distribution.
The data on particle size generated during the study is used to construct predictive models for the final particle size distribution that can be used to closely control product properties.
The monitoring of a second batch fluid bed granulation is shown in Figure 2. Here the data show the characteristic chord length values (x10; x50 and x90) of three successive batches. The operator can determine the batch to batch consistency of the production process and enhance process control to ensure product quality targets are met and maintained.
Figure 2. The in-line monitoring of three successive batch granulations (300kg) at a pharmaceutical production facility.
Figure 3 shows measurement in an apparatus for continuous granulation of pharmaceutical products, a Glatt Procell GF25.
Real time x10, x50, x90 measurements help manipulate parameters of the granulation process including input, output, rate of spraying and air flow rate to obtain the needed particle size in the initial batch period and subsequently to stabilize the process during continuous operation, preventing the formation of agglomerates.
The SFT probe was directly installed in the last chamber of the fluid bed to ensure a fast response to parameter changes. Figure 8 shows the image of an in-line particle size probe installed in a continuous fluid bed system.
Figure 3. Monitoring a continuous fluidized bed granulation process with an SFT probe
Figure 4. Image of an in-line particle size probe installed in a continuous fluid bed system.
Case Study: Using SFT to Track High Shear Granulation
During wet granulation in batch mode with a high shear granulator, as with a fluidized bed, the key issue is to accurately identify the optimal point at which to stop. In this case end point can be defined in terms of granule size continuous particle size measurement via the installation of a SFT probe enables real-time monitoring of the granulator towards the specified endpoint.
Figure 5 and 6 show the real time monitoring of a pilot scale high shear granulator and the image of an in-line particle size probe installed in a pilot scale high shear granulator.
Figure 5. Real-time monitoring of a pilot scale high shear granulator.
Figure 6. Image of an in-line particle size probe installed in a pilot scale high shear granulator.
Even though this environment is challenging for continuous analysis, as shown in Figure 6 the result show the probe’s ability to consistently and accurately measure chord length distribution (x10, x50 and x90) throughout the process.
Figure 7. The evolution of particle size distribution over the course of a wet high shear granulation.
Figure 7 shows the particle size distribution measured on a larger scale with a longer probe, during the course of a wet high shear granulation. The evolution of granulate size over a considerably short time frame is captured in this trend. Before the end point, evidence is presented of a reduction in x90 suggesting a decrease in the larger particle size population.
A demand for analytical solutions is created by the widespread application of granulation both wet and dry supporting effective process development, efficient process control, and precise endpoint detection. Since particle size is a defining characteristic for many granules, real-time particle size measurement offers substantial benefit.
Laser diffraction and SFT both offer continuous particle sizing for granulation applications. Laser diffraction is well-matched to dry granulation processes while SFT is particularly suitable for high shear wet granulation monitoring.
This information has been sourced, reviewed and adapted from materials provided by Malvern Panalytical.
For more information on this source, please visit Malvern Panalytical.