A method for grindability testing using the Scirocco disperser

Abstract

In the early stages of development of a new Active Pharmaceutical Ingredient (API), insufficient material quantity is available for addressing processing issues, and it is highly desirable to be able to assess processability issues using the smallest possible powder sample quantity. A good example is milling of new active pharmaceutical ingredients. For particle breakage that is sensitive to strain rate, impact testing is the most appropriate method. However, there is no commercially available single particle impact tester for fine particulate solids. In contrast, dry powder dispersers, such as the Scirocco disperser of the Malvern Mastersizer 2000, are widely available, and can be used for this purpose, provided particle impact velocity is known. However, the distance within which the particles can accelerate before impacting on the bend is very short and different particle sizes accelerate to different velocities before impact. As the breakage is proportional to the square of impact velocity, the interpretation of breakage data is not straightforward and requires an analysis of particle velocity as a function of size, density and shape. We report our work using an integrated experimental and CFD modelling approach to 2 evaluate the suitability of this device as a grindability testing device, with the particle sizing being done immediately following dispersion by laser diffraction. Aspirin, sucrose and -lactose monohydrate are tested using narrow sieve cuts in order to minimise variations in impact velocity. The tests are carried out at eight different air nozzle pressures. As intuitively expected, smaller particles accelerate faster and impact the wall at a higher velocity compared to the larger particles. However, for a given velocity the extent of breakage of larger particles is larger. Using a numerical simulation based on CFD, the relationship between impact velocity and particle size and density has been established assuming a spherical shape, and using one-way coupling, as the particle concentration is very low. Taking account of these dependencies, a clear unification of the change in the specific surface area as a function of particle size, density and impact velocity is observed, and the slope of the fitted line gives a measure of grindability for each material. The trend of data obtained here matches the one obtained by single particle impact testing. Hence aerodynamic dispersion of solids by the Scirocco disperser can be used to evaluate the ease of grindability of different materials.

Analysis of pin milling of pharmaceutical materials

“…Based on the specification of PicoPlex unit, the maximum particle feed size to be used for milling is 500 m due to the geometry and gap size between the pins. proposed by Bonakdar et al (2016a). The choice of materials has also been in line with their work.…”

“…The breakability assessment test was previously carried out on aspirin and -lactose monohydrate by Bonakdar et al (2016a). The same approach is applied here to paracetamol.…”

“…A number of test methods have been developed to analyse and assess the breakability of materials, ranging from quasi-static to dynamic stressing for both single and assemblages of particles in an attempt to describe the processes prevailing in a mill (Ghadiri et al, 2007;Olusanmi et al, 2011;Bonakdar et al, 2016a). The choice of technique and device depends on the dominant breakage mechanism of the mill (e.g.…”

“…Recently, Bonakdar et al (2016a) developed a novel breakability assessment technique using aerodynamic dispersion by the Scirocco disperser of the Malvern Mastersizer 2000. The analysis of Ali et al (2016) was used for calculating the particle impact velocity as a function of the applied pressure to the dispersion nozzle.…”

“…The experimental part of the work here has been carried out by milling aspirin, paracetamol and -lactose monohydrate. The breakage kernels of the materials have been developed using the approach of Bonakdar et al (2016a). EDEM simulation software package (DEM Solutions, Edinburgh, UK) is then used to analyse the particle dynamics in the mill.…”