You are on page 1of 6

Developing a method for dry

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:

Sample selection in terms of the


physical properties of the powder
which is to be tested.

Representative Sampling of the


material under test, such that the
sub-sample is characteristic of
the whole batch.

Users must also configure the sample


dispersion unit in order to achieve
reproducible results that actually
relate to the physical properties of the
powder itself, either in terms of the
agglomerated state or in a well
disperses state. This requires control
of the:

Sample Feed Rate of the sample


into the dispersion zone within
the dispersion unit.

Dispersion Energy or air


pressure used to cause
deagglomeration of the sample
within the air stream.

Measurement Time and other


analysis options such as
obscuration triggering and optical
properties.

become extremely large below 5


microns in size. In these cases wet
analysis may provide the only means
of ensuring reproducible particle
dispersion.

Powder Friability

Within this document it assumed that


the user is familiar with the basic
operation of a laser diffraction system.
The guidance relates specifically to
the Mastersizer 2000 system using
the Scirocco 20000 dry powder
feeder. However, the method
development steps described here
can be applied to the dry powder
feeder systems shipped with other
Malvern products. Note that guidance
on the selection of optical properties
is given elsewhere.

The method of dispersion within a dry


powder feeder is similar to that seen
in an air jet mill. Particle-particle
collisions and collisions between the
particles and the walls of the
dispersion unit aid dispersion.
However, these processes can also
cause particle attrition. This is often
seen for pharmaceutical materials,
especially if the particles are needlelike in morphology. For such materials
it may not be possible to bring about
dispersion without considerable
particle break-up occurring. In such
cases wet analysis is preferred.

Sample Selection

Sample Toxicity

Before selecting a dry method for


particle size analysis it is important
that the characteristics of the sample
under test are considered.

During a dry measurement the


powder under test is carried in an air
stream through the laser diffraction
measurement zone and is then
collected in an industrial vacuum
cleaner system. The Scirocco 2000
dry powder system provided with the
Mastersizer 2000 uses an enclosed
measurement cell that always
operates at a slight negative pressure,
aiding powder containment. The filter
system on the vacuum cleaner is also
HEPA-rated. However, it is still
possible for small amounts of material
to escape into the environment,
especially during cleaning of the
system. This may not be acceptable
for some toxic materials or for
pharmaceutical products that are
extremely active. For these materials
wet analysis would allow exposure to
be more easily controlled.

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

Mastersizer 2000 application note

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

particle loading ensures this is


achieved within the venturi system.

During SOP development, it is


important to consider how the
dispersion unit settings affect the
measured particle size. This includes
the sample feed rate and the air
pressure used to cause dispersion.
Other parameters such as the overall
measurement time should also be
considered.

Sample Tray Configuration


The General Purpose dry powder
feeder tray for the Scirocco 2000
allows the user to the set the gate
width at the end of the tray in order to
help control the feed rate.
Examination of how the material
under test flows can help in setting
this width. If the material under test is
very free flowing it may be helpful to
narrow the gate spacing on the feed
tray. This will prevent the material
over-loading the venturi. However,
this may not work if the material is
cohesive as the gate may become
blocked. The gate aperture should be
increased in such a situation and the
feed rate reduced to achieve the
required flow rate and measurement
obscuration.

Controlling the Sample Feed


During dry powder feeder
measurements it is important to
ensure that the sample feed into the
venturi is constant and set at a high
enough value to yield a reasonable
measurement obscuration. Using too
high an obscuration can lead to
multiple scattering and an underreporting of the particle size. It is also
true that the dispersive effort yielded
within the venturi system depends not
only on the air pressure but also the
particle loading. A high or uneven
material feed can therefore lead to
poor or irreproducible dispersion,
affecting the precision of any particle
size measurements.
Feed Rate Settings
The measurement obscuration is the
best indicator of whether the correct
feed rate has been selected for the
dry powder feeder. For the
measurement of free-flowing
materials or large particles the feed
rate should be set to provide an
obscuration of between 1% and 6%.
This will ensure that a good signal-tonoise ratio is achieved, yielding
reproducible results. For fine particles
or cohesive materials (e.g. cement) a
lower obscuration in the range from
0.5% to 3% is generally required. This
reflects the fact that for these
materials the maximum dispersive
effort is required at any given
pressure to ensure reproducible
particle dispersion. Limiting the

Mastersizer 2000 application note

For Scirocco 2000 users additional


micro and macro volume sample trays
are available that can be used instead
of the General-Purpose tray. These
have a fixed gate width and are
designed to provide a morecontrollable sample flow rate. This is
particularly useful when measuring
fine particles.
An additional feature of Malvern dry
powder feeders is a fine-mesh basket
that can be positioned above the
venturi. Ball bearings can be placed in
this basket in order to even out any
fluctuations in the particle flow.
However, use of ball bearings is not
advised for fine powders as the
system will quickly become clogged
with powder and will be difficult to
clean. In such cases measurements
should be repeated with no ball
bearings or with the wider diameter
mesh basket in order to achieve a
steady powder flow through the
system. The ideal is to select a flow
which achieves a steady obscuration
(with no surging) throughout the entire
measurement duration.

MRK524-01

Although setting of the obscuration


limits is important, they should not be
used to correct for a poor feed rate.
The reason for this is shown in figure
1, which shows how the obscuration
limits are applied for two different
measurement situations.
Case A in figure 2 the initial part of the
measurement is lost due to the fact
that the obscuration limits are set too
high. However, when the sample flow
does increase it is clear that the feed
rate has not been correctly adjusted.
The obscuration quickly rises out of
range before falling towards the end
of the measurement. This
combination of poor obscuration limits
and incorrect feed rate settings yields
a measurement where less than 1/3
of the sample has been measured.
This will have implications as far as
the measurement accuracy is
concerned, especially if the limits of
the distribution are of importance.
Case B shows the ideal situation for
dry measurement. At the beginning of
the measurement the obscuration
settings ensure that the noisy data
observed at very low obscurations is
not collected. However, the feed rate
is such that the obscuration quickly
enters the desired range and remains
in range for most of the measurement
time until the sample concentration
becomes too low. In this case most of
the sample has been measured,
ensuring good measurement
accuracy. This also follows the
guidance within ISO13320-1, which

states that the entire sample must be


measured if representative results are
to be obtained.
Material flowing but no
measurements being
performed

A
Lower limit
Obscuration
Upper limit

B
Lower limit

Time

Figure 1 Obscuration control during


dry powder measurements.
109
108
107
106
105
104
103

Adhesion

102
101
100
10-1
10-2
10-3
10-4
10-5

10-2 10-1

100 101 102


Particle size ()

103

It is therefore important that the


particle size is measured as a function
of pressure as part of SOP
development.

Dispersion Requirements

Upper limit

Ratio of force to gravity force

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

Figure 2. Particle adhesion as a


function of particle size [3].

Air pressure selection


The effect of dispersion air pressure is
probably one of the most poorly
understood aspects of dry powder
measurement using laser diffraction.
However, as stated in ISO13320-1, if
the effect of dispersion pressure is not
investigated it is impossible to
determine whether complete
dispersion has been achieved or
whether particle attrition has occurred.

Mastersizer 2000 application note

Dispersion of agglomerates occurs


when the adhesion forces which exist
between the particles in the sample
are overcome. At large particle sizes
(>10 microns) these forces are quite
small (figure 2), thus dispersion can
be achieve by simple agitation of the
sample. However, below 10 microns
the forces of attraction between
particles can be huge, ranging from
1
5
10 g at 10 microns to 10 g at 0.1
microns. Thus, a significant amount of
energy is required to achieve
dispersion when measuring particles
within this range.
A dry powder feeder is similar in
design to an air jet mill. Particles
traveling through the venturi are
subjected to high accelerations, with
the applied shear being related to the
dispersant pressure setting. This,
coupled with particle-particle and
particle-wall collisions, helps to
disperse agglomerates. The key to a
good dry measurement is to apply a
high enough pressure to cause
particle dispersion. However care
must be taken when measuring friable
materials as use of high dispersion
pressures may result in fracture of the
material and the milling of the product.
The only way to assess whether
dispersion or milling is occurring is to
perform a pressure titration. This
simply involves measuring the particle
size as a function of pressure in order
to determine which setting is most
suitable. Selection of the correct
pressure should be achieved by
comparing the dry results against a
well-dispersed result obtained using
wet dispersion (see ISO13320-1
section 6.2.3). In all cases it is true
that a dry result can never been finer
than one obtained using the correct
wet dispersion method this relates
to the fact that the energy available

MRK524-01

for dispersion in a slurry is much


higher than that seen when particles
are placed under shear in an air
stream.

will ensure that no sampling bias is


observed due to the method of
delivery of the sample into the
measurement zone (see ISO13320-1
section 6.2.3).

Measurement Times

Correct selection of the obscuration


settings will ensure measurement of
the entire sample. A time-out can be
set so that, when the obscuration falls
below the desired range, the
instrument will wait a specified period
before terminating the measurement.
This will allow any problems with
intermittent feed to be overcome,
ensure the entire batch is
characterized.

When setting up a dry measurement


SOP it is important that to ensure that
the entire sample placed on the dry
powder feeder tray is measured. This
Dv10

Dv50

Dv90

90
80

Size / Microns

70
60
50
40
30
20
10
0
0

Pressure / Bar

Figure 3: Pressure titration for an iron


powder sample.
Dry (4 bar)

Wet (after sonication)

10
9
8

Volume (%)

7
6
5
4
3
2
1
0
0.01

0.1

10

100

1000

Particle Size / Microns

Figure 4: Comparison of the particle


size distribution measured at 4bar with
that reported using wet dispersion.
Dry (0 bar)

Wet (no sonication)

10
9

Beyond this, it is best that several


repeat measurements of short
duration are obtained during the
measurement period. Typically an
individual measurement time of
between 2 and 5 seconds should be
used, with enough repeat
measurements to allow the entire
sample to be measured. The average
across the results obtained can then
be taken. One advantage with this
method is that the measurements
acquired at the beginning and end of
the measurement processes can be
discarded from the averaging process
should they show poor signal-to-noise
due to low sample concentrations. It is
also possible to determine if sample
segregation occurs during the
measurement. This would then
highlight the need for a good sampling
methodology as, if segregation occurs
within the dispersion unit, it is also
likely to occur with the process from
which the sample is extracted.

Method Development
Examples

Volume (%)

7
6
5
4
3

Metal Powder Measurements

2
1
0
0.01

0.1

10

100

1000

Particle Size / Microns

Figure 5: Comparison of the particle


size distribution measured at 0bar with
that reported prior to sonication using
wet dispersion.

Figure 3 shows the pressure-size


titration carried out for a robust iron
powder sample. As can be seen, a
large decrease in particle size is
observed in moving from 0bar to 1bar
pressure. Beyond this, a roughly

Mastersizer 2000 application note

linear decrease in size is observed


with pressure. However, at this point it
is unclear if the observed size
decrease is related to dispersion or
particle break-up. This can only be
determined by comparing the dry
measurements with those obtained
using a wet dispersion method.
Figure 4 shows a comparison of the
result obtained using a pressure of
4bar with that obtained using wet
dispersion. In this case excellent
agreement is obtained, showing that
complete dispersion has been
achieved within the dry powder
feeder.
Good agreement is also observed for
the un-dispersed sample in this case.
Figure 5 shows a comparison of the
size distribution measured dry at
0.1bar pressure against the wet result
recorded before ultrasonic dispersion.
This provides additional evidence as
to the nature of the dry dispersion
process (low pressure =
agglomerated; high pressure =
dispersed). However, the key here is
the comparison of the 4bar result
against the well-dispersed wet result
as far as method development is
concerned.

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

Figure 6: Pressure titration for a fragile


powder sample.
Dry (0.2 bar)

Wet (after sonication)

16
14

Volume (%)

12
10
8
6
4
2
0
0.01

0.1

10

100

1000

Particle Size / Microns

Figure 7: Comparison of the particle


size distribution reported at 0.2bar with
that obtained using wet dispersion.

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.

Again, comparison with wet


dispersion allows the correct dry
dispersion pressure to be
determined. A good wet-dry
correlation is observed at 0.5bar in
the case (figure 9). Beyond this
pressure the fine fraction is overreported.

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

Mastersizer 2000 application note

presence of material larger than that


seen within the wet result is reported.
However, there is also an increase in
fines compared to the wet result, due
to particle break-up. This provides a
good example of the fact that
dispersion and break-up occur
simultaneously rather than as
separate process. Increasing the
pressure to 4bar does aid dispersion
of the larger material. However,
increased break-up is also observed.
As such, dry characterization of this
material is not recommended.
Dv10

Dv50

Dv90

100
90
y = -3.2x + 89.9

80
70

Size / Microns

Dv10
35

Within the measurement zone the


powder slows down, as the vacuum
extraction velocity is always less than
the powder exit velocity. The fines
within the sample slow more quickly
compared to the coarse particles as
they have a lower inertia. This causes
a velocity bias to be observed, where
the fine fraction is over-sampled (the
fine particles are present in the
measurement zone for a
proportionally longer period compared
to the coarse particles due to their
lower velocity). This bias is seen on
all dry powder feeder systems
regardless of manufacturer. The
enclosed air cell developed for the
Scirocco 2000 system helps
minimize the observed bias.
However, it is never completely
negated. This explains the trend
seen in figure 8 the exit velocity
increases as the pressure is
increased, leading to an increase in
the observed velocity bias and a shift
towards a finer result.

60
50
y = -2.6x + 48.7

40
30
20

y = -2.0x + 20.9

10
0
0

Pressure / bar

Figure 8: Pressure titration for a freeflowing powder sample.


Dry (0.5 bar)

Wet (after sonication)

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

Particle Size / Microns

Figure 9: Comparison of the particle size


distribution reported at 0.5bar with that
obtained using wet dispersion.

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

developed, ensuring good batch-tobatch reproducibility. This, in turn,


increases the sensitivity of the size
measurement to changes in the
material properties.
Dv10

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

[3] Ed. C N Davies (1966), Aerosol


Science, Academic Press, London
and New York

350

Size / Microns

300
250
200
150
100
50
0
0

Pressure / bar

Figure 10 - Pressure titration for a


fragile crystalline material.
Dry (3 bar)

Wet (after sonication)

16
14

Volume (%)

12
10
8
6
4
2
0
0.01

0.1

10

100

1000

Particle Size / Microns

Figure 11 - Comparison of the


particle size distribution reported at
3bar with that obtained using wet
dispersion.

Malvern Instruments Ltd


Enigma Business Park Grovewood Road Malvern Worcestershire UK WR14 1XZ
Tel: +44 (0)1684 892456 Fax: +44 (0)1684 892789
Malvern Instruments Worldwide
Sales and service centers in over 50 countries for details visit www.malvern.co.uk/contact

more information at www.malvern.co.uk

Mastersizer 2000 application note

MRK524-01

You might also like