Pharmaceutical
Small Doses Analysis using GranuHeap
When a powder is poured onto a surface, a heap is formed. It is well known that both the repose angle and the heap shape strongly depend on grain properties. In particular, a cohesive powder forms an irregular heap while a non-cohesive powder forms a regular conical heap.
Introduction
Theoretical Framework
Granular materials and fine powders are widely used in industrial applications. To control and to optimize processing methods, these materials have to be precisely characterized. The characterization methods are related either to the properties of the grains (granulometry, morphology, chemical composition, …) and to the behaviour of the bulk powder (flowability, density, blend stability, electrostatic properties, …).
However, concerning the physical behaviour of bulk powder, most of the techniques used in R&D or quality control laboratories are based on old measurement techniques. During the last decade, we have updated these techniques to meet the present requirements of R&D laboratories and production departments. In particular, the measurement processes have been automatized and rigorous initialization methods have been developed to obtain reproducible and interpretable results. Moreover, the use of image analysis techniques improves the measurements precision.
A range of measurement methods has been developed to cover all the needs of industries processing powders and granular materials. However, in this application note, we will be focused on the GranuHeap instrument.
GranuHeap
When a powder is poured onto a surface, a heap is formed. It is well known that both the repose angle and the heap shape strongly depend on grain properties. In particular, a cohesive powder forms an irregular heap while a non-cohesive powder forms a regular conical heap. Therefore, a precise measurement of the heap shape provides useful information about the physical properties of the powder sample.
The GranuHeap instrument is an automated heap shape measurement method based on image processing and analysis. A powder heap is created on a cylindrical support.
LEARN MORE ABOUT THE GRANUHEAP
In order to obtain reproducible results, an initialization tube with an internal diameter equal to the circular support is installed on the support. After filling the initialization tube by hand with a fixed volume of powder (typically 100 ml), the tube goes up at the constant speed. Thereby, the powder is flowing from the tube to form a heap on the cylindrical support. A controlled rotation of the support allows obtaining different heap projections corresponding to different heap orientations. A custom image recognition algorithm determines the position of the powder/air interface.
The repose angle refers to the angle of the isosceles triangle with the same surface than the powder heap projected image. This isosceles triangle corresponds to the ideal cohesiveness heap shape. The repose angle is computed for each image, i.e. for each heap orientation. Afterward, an averaged value is computed.
In general, the lower the repose angle is, the better the powder flowability is. The deviation between the real heap interface and the isosceles triangular heap provides the static cohesive index. The static cohesive index is computed for each image, i.e. for each heap orientation. Afterwards, an averaged value is computed. This static cohesive index is close to zero for a non-cohesive powder and increases when the cohesive forces inside the powder strengthen.
The next Table summarizes the empirical relation between the results obtained with GranuHeap instrument and powder flowability:
| Flow | Repose Angle (°) | Static Cohesive Index |
| Excellent | 25-30 | < 0.2 |
| Good | 31-35 | 0.3 - 0.5 |
| Fair | 36-40 | 0.6 - 0.8 |
| Passable | 41-45 | 0.9 - 1.2 |
| Poor | 46-55 | 1.3 - 1.7 |
| Very Poor | 56-65 | 1.8 - 2.4 |
| Very very poor | > 66 | > 2.5 |
Experimental Setup
Material
For this application note, three different powders were selected: FlowLac 100, GranuLac 70 and InhaLac 400. They are lactose samples provided by Meggle Pharma. GranuLac types consist of fine, sharp-edged lactose particles, having cohesive powder properties that can be beneficial during granulation processes. InhaLac is a high quality crystalline lactose powder, designed for DPIs.
FlowLac powder is produced by spray-drying a suspension of fine milled alpha-lactose monohydrate crystals in a solution of lactose. When lactose in solution is spray-dried, a rapid removal of water is taking place, whereby amorphous, non-crystalline lactose is formed in addition to crystalline lactose.
Table 1: Lactose Properties (supplier data)
Methods
For each experiment with the GranuHeap instrument, the 40 / 30 / 20 and 10mm diameter supports were selected. 16 pictures were taken during the heap rotation (1 picture each 11.25°) to increase measurements accuracy. At the end of analysis, one final picture is taken to check the pile integrity when measurement is done.
All experiments were carried under the same humidity/temperature values (30% RH and 21°C). All tests were repeated five times. The excipients were stocked in our laboratory during several months. Therefore, the history of the samples is unknown and their properties could not correspond to the specifications of the producers for fresh powders.
LEARN MORE ABOUT THE GRANUHEAP
Experimental Results
The following figure represents the Angle of Repose obtained with every powder and support diameter. Straight lines do not correspond to a model, they are just displayed to guide the eye. Error bars are displayed (they correspond to the standard deviation on the dynamic angle of repose obtained for the five repeatability tests):
Figure 1: Angle of repose versus support diameter for the three lactose powders - Straight lines are present only to guide the eye
Figure 1 allows to conclude about the support influence on the static Angle of Repose measurement. Indeed, we can see that for powders with a “poor” flowability (Angle of Repose bellow 55°), the lower the support diameter, the lower the Angle of Repose. Nevertheless, for powders with a “very very poor” flowability (Angle of Repose above 66°), there is no support influence on the results (if we take into account the error bars).
However, for one diameter, the trends in terms of powders flowability classification is the same. Thus, powders classification can be easily achieved with great accuracy (average error close to 3.5%). Finally, since the heap shape analysis is relative measurements, it allows to conclude that changing the heap support will not directly affect the analysis.
LEARN MORE ABOUT THE GRANUHEAP
Conclusions
- The GranuHeap instrument allows to measure powder flowability with a wide range of support and with a great accuracy (average error close to 3.5% for lactose powders);
- There is a slight support influence on measurements. However, for one support, the flowability trends are the same. Therefore, powders classification is unchanged.
References
Cascade of granular flows for characterizing segregation, G. Lumay, F. Boschin, R. Cloots, N. Vandewalle, Powder Technology 234, 32-36 (2013).
Combined effect of moisture and electrostatic charges on powder flow, A. Rescaglio, J. Schockmel, N. Vandewalle and G. Lumay, EPJ Web of Conferences 140, 13009 (2017).
Compaction dynamics of a magnetized powder, G. Lumay, S. Dorbolo and N. Vandewalle, Physical Review E 80, 041302 (2009).
Compaction of anisotropic granular materials: Experiments and simulations, G. Lumay and N. Vandewalle, Physical Review E 70, 051314 (2004).
Compaction Dynamics of Wet Granular Assemblies, J. E. Fiscina, G. Lumay, F. Ludewig and N. Vandewalle, Physical Review Letters 105, 048001 (2010).
Effect of an electric field on an intermittent granular flow, E. Mersch, G. Lumay, F. Boschini, and N. Vandewalle, Physical Review E 81, 041309 (2010).
Effect of relative air humidity on the flowability of lactose powders, G. Lumay, K. Traina, F. Boschini, V. Delaval, A. Rescaglio, R. Cloots and N. Vandewalle, Journal of Drug Delivery Science and Technology 35, 207-212 (2016).
Experimental Study of Granular Compaction Dynamics at Different Scales: Grain Mobility, Hexagonal Domains, and Packing Fraction, G. Lumay and N. Vandewalle, Physical Review Letters 95, 028002 (2005).
Flow abilities of powders and granular materials evidenced from dynamical tap density measurement, K. Traina, R. Cloots, S. Bontempi, G. Lumay, N. Vandewalle and F. Boschini, Powder Technology, 235, 842-852 (2013).
Flow of magnetized grains in a rotating drum, G. Lumay and N. Vandewalle, Physical Review E 82, 040301(R) (2010).
How tribo-electric charges modify powder flowability, A. Rescaglio, J. Schockmel, F. Francqui, N. Vandewalle, and G. Lumay, Annual Transactions of The Nordic Rheology Society 25, 17-21 (2016).
Influence of cohesives forces on the macroscopic properties of granular assemblies, G. Lumay, J. Fiscina, F. Ludewig and N. Vandewalle, AIP Conference Proceedings 1542, 995 (2013).
Linking compaction dynamics to the flow properties of powders, G. Lumay, N. Vandewalle, C. Bodson, L. Delattre and O. Gerasimov, Applied Physics Letters 89, 093505 (2006).
Linking flowability and granulometry of lactose powders, F. Boschini, V. Delaval, K. Traina, N. Vandewalle, and G. Lumay, International Journal of Pharmaceutics 494, 312–320 (2015).
Measuring the flowing properties of powders and grains, G. Lumay, F. Boschini, K. Traina, S. Bontempi, J.-C. Remy, R. Cloots, and N. Vandewall, Powder Technology 224, 19-27 (2012).
Motion of carbon nanotubes in a rotating drum: The dynamic angle of repose and a bed behavior diagram, S. L. Pirard, G. Lumay, N. Vandewalle, J-P. Pirard, Chemical Engineering Journal 146, 143-147 (2009).
Mullite coatings on ceramic substrates: Stabilisation of Al2O3–SiO2 suspensions for spray drying of composite granules suitable for reactive plasma spraying, A. Schrijnemakers, S. André, G. Lumay, N. Vandewalle, F. Boschini, R. Cloots and B. Vertruyen, Journal of the European Ceramic Society 29, 2169–2175 (2009).
Rheological behavior of β-Ti and NiTi powders produced by atomization for SLM production of open porous orthopedic implants, G. Yablokova, M. Speirs, J. Van Humbeeck, J.-P. Kruth, J. Schrooten, R. Cloots, F. Boschini, G. Lumay, J. Luyten, Powder Technology 283, 199–209 (2015).
The flow rate of granular materials through an orifice, C. Mankoc, A. Janda, R. Arévalo, J. M. Pastor, I. Zuriguel, A. Garcimartín and D. Maza, Granular Matter 9, p407–414 (2007).
The influence of grain shape, friction and cohesion on granular compaction dynamics, N. Vandewalle, G. Lumay, O. Gerasimov and F. Ludewig, The European Physical Journal E (2007).