Better particle characterisation means better processing

Paul Boughton

Fast and cost-effective particle characterisation leads to more consistent and less expensive manufacturing for the chemical industry. Eugene McCathy reports.
Mettler Toledo has launched its new inline particle system characterisation tool ParticleTrack E25.
Modifying focused beam reflectance technology (FBRM) for use in settings where pneumatic motors are impractical, the fully electric ParticleTrack E25 measures aqueous particle and droplet systems for the chemical and other industries.
This probe-based technology eliminates sampling’s measurement variability for simpler, faster and more cost-effective system characterisation, as well as the more consistent and less expensive manufacturing outcomes it promotes (Fig. 1).
Based on traditional FBRM technology yet requiring no air/gas supply, this robust FBRM probe allows real-time product-quality optimisation, greater formulation stability, and enhanced processing whether particle systems are being observed in two-litre beakers, 20,000-litre vessels, or pipeline flow. This versatility and ease-of-use is helping to put FBRM technology in the hands of labs and production environments in industries where it has historically been considered a luxury.
Now, those working in non-explosive environments in almost any industry can access FBRM’s ability to optimise processes in real-time. This includes FBRM advances such as the ability to detect and correct for particles that are ‘stuck’ to the probe and enhanced measurement consistency over a wider dynamic range. These improvements maximise sensitivity and data integrity and encourage more intuitive data analysis.
ParticleTrack E25 is ideal for measuring modern manufacturing processes such as crystallisation and precipitation; homogenisation and emulsification; and solid/liquid or liquid/solid separations including flocculation, coalescence, and flotation.
In a separate development, Mettler Toledo has published its latest, free, downloadable white paper. ‘Recent advances for seeding a crystallisation process: a review of modern techniques’ explores crystallisation experiments that, coupled with advanced seeding techniques and real-time in situ process feedback, provide results which significantly improve yields and reduce manufacturing costs.
Seeding has become a critical and widely-used step to optimise crystallisation behaviour, process efficiency, and product quality. However, a non-ideal seeding protocol can result in inconsistent filtration rates, drying times, yields, bulk density, flow properties and particle size distribution—any of which can disrupt downstream processing, potentially resulting in costly rework or even expensive product loss.
The white paper details both general seeding theory and use of inline particle measurement tools such as FBRM, particle vision and measurement (PVM), and ATR-FTIR (ReactIR). Results include significantly improved fine particle counts which eliminated the need for post-crystallisation milling. In practical application, this benefit has been shown to shorten production schedules for faster time-to-market - an essential ingredient in cost-effective chemical and pharmaceutical manufacturing in today’s highly competitive global marketplace.
The white paper can be downloaded HERE  [Page Break]
Granulation processes

The Parsum in-line particle sizing probe from Malvern Instruments is proving its value as a process analytical technology (PAT) instrument in granulation research being conducted at Ghent University in Belgium.
Professor Thomas De Beer’s PAT group at the university is successfully using the instrument to continuously monitor granulation processes and to develop effective automated strategies for process control.
The PAT group focuses on identifying robust and relevant PAT tools for the chemical and pharmaceutical industries. The team researches how these can be applied to improve manufacturing efficiency. Granulation trials have shown that real-time particle size measurements, in combination with other analytical data, support consistent production of granules to a defined specification.
De Beer said: “In our research we look at all aspects of PAT. We focus not only on assessing different technologies and instrumentation for monitoring, but on applying the resulting data to process control. Using Parsum we have tracked the evolution of particle size in real time during fluidised bed granulations. The data provide detailed information during design of experiment studies and enable us to develop models for real-time batch evaluation. These models help drive effective automated process control and reduce batch release times, both of which are important goals for processors.”
PAT is playing a pivotal role in achieving the fine chemical and pharmaceutical industries’ stated aims of moving away from batch operation and off-line monitoring towards continuous, integrated processing and real-time release. Granulation is a unit operation that is used widely in pharmaceutical processing, particularly in tablet production, but its control can be challenging.
De Beer’s research shows that by correlating particle size data - and other process variables such as binder addition rate and inlet air temperature - with granule quality defined in terms of density, it is possible to develop predictive process models. These can be used to define and control processing conditions to deliver a successful outcome.
The rugged Parsum probe measures particle size across the size range 50-6000 microns using the technique of spatial particle velocimetry. Available in a number of different probe lengths it is designed specifically for in-process use and can be installed directly into a line or vessel for real-time monitoring. With a number of in-built features that prevent fouling, the Parsum delivers continuous performance even for demanding applications such as wet granulation, and is easily integrated in automated control hierarchies.

Powder characterisation

New from Hosokawa Micron is the Hosokawa PT-X powder characteristics tester, the latest version of the well-known laboratory unit which is used to determine powder characteristics when designing powder handling and processing systems.
The new unit been updated with a number of features to make it easier to use and more operator friendly. The new design allows the unit to be used in conjunction with computers for data recording, delivering a clear visual display of analysis results to enable the operator to evaluate the results simply and quickly.
All seven powder characteristics that help in the design and control of powder handling and processing systems can be measured by the PT-X unit: angle of repose, compressibility, angle of spatula, cohesion, angle of fall, dispersibility, and angle of difference. In addition three auxiliary values - aerated bulk density, packed bulk density and uniformity - can also be evaluated in order to determine results for the flowability and floodability of dry powders.
The new PT-X looks very different from previous versions and is more compact in design. The unit offers computer control via a touch screen 12.5 inch tablet PC using a core i5 processor with Windows 7 Professional operating system which can reduce analysis time. Reduced operator intervention ensures analysis accuracy and repeatability.
The unit’s inner wall forms part of the structure making the PT-X easier to clean and an optional integrated HEPA filter for dust protection is available, as is a vacuum cleaner.
In a separate development, close cooperation with one of the world’s largest pharmaceutical companies has enabled Hosokawa Micron to develop a novel contained particle size reduction facility that is suitable for flexible milling down to ultrafine particles of active pharmaceutical ingredients (APIs) at R&D, pilot scale and small scale production volumes.
The contained API particle size reduction facility includes three mills plus a lump breaker, three material feed options and operator exposure levels of <1μg/m3. Manufactured to cGMP design and incorporating full SCADA control the system is the first size reduction facility of its kind to offer such high levels of ‘complex but not complicated’ operational flexibility that is crucial in today’s fast moving and competitive market.
“Hosokawa Micron engineers have worked closely with the customer’s production and engineering teams to develop this new dimension in flexible API processing with every opportunity taken to deliver a long term, ‘future proof’ processing facility. We have been able to use existing equipment and associated performance data to deliver to the customer a highly customised processing solution as a result of our longstanding working partnership,” said Mike Coffey, pharma team leader, Hosokawa Micron.[Page Break]

Particle testing services
Particle size, particle concentration and other physical characterisation analyses are critical to many environmental applications.
Regulatory agencies in the environmental sphere demand strict compliance to standards and discharge regulations. Physical testing of samples for parameters such as particle size and concentration can give insight to the process control engineer on how effective and compliant a discharge handling system is operating. Particulate loading from both air emissions and waste water discharge are monitored in many industry sectors and Particle Technology Labs (PTL) testing provides valuable supporting data in this monitoring process.
Evaluation of filter efficiency by analysis of pre- and post-filtration samples for particle size and concentration has proven useful to numerous clients. Values such as PM10, PM2.5, total suspended solids concentration, pH, conductivity and particle size distribution are just some of the commonly referenced values by regulatory agencies and process engineers. PTL has provided accurate and reliable testing for these parameters since its inception.
In addition, the company’s analytical staff has years of experience designing test methods and performing analysis for cosmetic, skin care, fragrance and personal hygiene samples. Whether a customer needs a third-party verification, routine QC confirmation, stability studies or one time testing, PTL will create a project to meet individual needs.  
Applications include the size and shape of cosmetic enhancers (glitter particles for example) in a final product, droplet size from spray nozzles/atomisers and particle size of emulsion particles comprising creams/lotions. In addition, the particle size of powdered cosmetics is of tremendous importance in how they flow, cover and can directly affect their appearance as well as the user’s skin.