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powder analysis
Introduction
For materials that are produced or
used as dry powders it is often
necessary to carry out particle size
analysis in the dry state. Dry analysis
provides a means of analyzing
samples that are soluble in common
solvents, such as some
pharmaceuticals actives. It also
provides a route to analyzing
materials where hydration may affect
the particle size, for example cement
or some biopolymers used as food
additives.
This application note aims to provide
users with an idea of the important
parameters that should be considered
as part of method development when
defining a Standard Operating
Procedure (SOP) for measuring dry
powders using laser diffraction. Dry
measurements can appear to be easy
to set up. However, it is important that
the following factors associated with
the sample are considered if realistic
measurements are to be made:
Powder Friability
Sample Selection
Sample Toxicity
Ease of Dispersion
In a dry measurement, dispersion is
achieved through a two-stage
process. First, the particles are
entrained a compressed air stream.
They then experience rapid
accelerations as the air stream is
passed though a venturi. Although the
shear applied during this process
provides enough energy to break
apart large particles or loose
agglomerates, it is not possible to
disperse sticky materials.
Measurement of fine particles can
also be difficult using dry analysis.
This is due to the fact that the forces
of attraction between particles
MRK524-01
Sample Size
In a dry powder feeder the sample is
only measured once before being
collected by the vacuum cleaner
system. For small sample volumes
this limits the amount of data that can
be collected by the optical system.
Thus, although the measurement of
milligram powder quantities is
possible, the measurement
reproducibility obtained may not be
good. Use of a wet dispersion method
can improve measurement
reproducibility in these situations as
the sample can be recirculated
through the measurement zone,
allowing many measurements to be
collected for the same sample. It is
also possible to optimize the
dispersion conditions during the
measurement for wet analysis.
Representative
Sampling
The way that the sample is withdrawn
from the bulk material for analysis is
one of the most important aspects of
particle size analysis. This is
particularly true if large particles (> 70
microns is size) are present in the
sample. Laser diffraction is a volumebased measurement technique and is
therefore sensitive to small changes
in the amount of large material in the
sample. This is because coarse
particles occupy a large volume
compared to smaller particles (one
100 micron particle has the same
volume as one million 1 micron
particles and will therefore give the
same scattering response). A guide to
how sampling can be controlled is
[1]
given elsewhere . If sampling is
controlled it should be easy to obtain
measurement-to-measurement
reproducibility within the limits defined
in ISO13320-1[2], the ISO standard for
laser diffraction measurements (within
3% at the D(v,0.5) and within 5% at
the D(v,0.1) and D(v,0.9)). If sampling
is not controlled then measurementto-measurement variations of up to
20% can be observed.
Measurement
Parameter Selection
MRK524-01
A
Lower limit
Obscuration
Upper limit
B
Lower limit
Time
Adhesion
102
101
100
10-1
10-2
10-3
10-4
10-5
10-2 10-1
103
Dispersion Requirements
Upper limit
Obscuration Settings
Obscuration filtering is used during
the laser diffraction measurement to
reject data where the sample loading
is either too high or too low. Correct
setting of the obscuration filter options
within the software is key if
reproducible results are to be
obtained. Although much can be done
to ensure an even feed rate
throughout the measurement, it is
important to ensure that any data
collected outside of the desired
measurement range is rejected.
104
MRK524-01
Measurement Times
Dv50
Dv90
90
80
Size / Microns
70
60
50
40
30
20
10
0
0
Pressure / Bar
10
9
8
Volume (%)
7
6
5
4
3
2
1
0
0.01
0.1
10
100
1000
10
9
Method Development
Examples
Volume (%)
7
6
5
4
3
2
1
0
0.01
0.1
10
100
1000
Particle Break-up
Figure 6 shows the pressure titration
data for a relatively fragile powder
containing some plate-like particles. In
this case a comparatively large
change in size is seen between 0bar
and 1bar, followed by a gradual
change in size as the pressure is
further increased. The steep section
of this curve may represent dispersion
or, on the other hand, may represent
milling of material. Comparison with a
well-dispersed wet result allows the
dry dispersion process to be
understood. A good wet-dry
correlation is observed at 0.1bar
(figure 7), suggesting that particle
milling occurs beyond this pressure.
The change in slope of the pressure
titration curve at 1bar signifies the
MRK524-01
Dv50
Dv90
30
Size / Microns
25
20
15
10
0
0
Pressure / bar
16
14
Volume (%)
12
10
8
6
4
2
0
0.01
0.1
10
100
1000
Free-flowing powder
measurements
Figure 8 shows the pressure-size
titration for a free-flowing powder
sample. In this case a constant
decrease in particle size is observed
across the entire range. The slope of
the curve yields change in the Dv50 of
around 2.6 microns per 1bar increase
in pressure. This is unlikely to be due
to particle break-up or dispersion.
Instead it is related to the way the
particles are presented to the
measurement zone within the dry
powder feeder.
Particles exiting the venturi in the dry
powder feeder travel at high speed.
Measurement of Fragile
Crystallites
Figure 10 shows a pressure titration
obtained for fragile crystalline
material. For this material a constant,
large decrease in particle size is
observed as a function of pressure.
This is most obvious for the reported
Dv90 value, where a shift from almost
350 microns to less than 230 microns
is observed in moving from 1bar to
4bar dispersion pressure.
Comparison of the size distribution
report at 3bar dispersion pressure
with a well-dispersed wet result is
shown in figure 11. It is clear that at
this pressure full dispersion is not
observed. This explains why the
Dv50
Dv90
100
90
y = -3.2x + 89.9
80
70
Size / Microns
Dv10
35
60
50
y = -2.6x + 48.7
40
30
20
y = -2.0x + 20.9
10
0
0
Pressure / bar
16
14
12
Volume (%)
point where maximum particle breakup has been achieved. The change in
size beyond this point is associated
with the change in particle velocity as
the dispersion pressure increases, as
explained in the next example.
10
8
6
4
2
0
0.01
0.1
10
100
1000
Summary
The development of a dry
measurement method requires the
user to explore the way the material is
sampled, the flowability of the sample
under test as well as how the sample
reacts to increases in the dispersion
effort used to bring about
deagglomeration. By controlling each
of these a robust method can be
MRK524-01
Dv50
References
[1] Sampling for Particle Size
Analysis. Malvern Application Note:
MRK456.
[2] ISO13320 (1999). Particle Size
Analysis - Laser Diffraction Methods.
Part 1: General Principles.
Dv90
400
350
Size / Microns
300
250
200
150
100
50
0
0
Pressure / bar
16
14
Volume (%)
12
10
8
6
4
2
0
0.01
0.1
10
100
1000
MRK524-01