Basic principles of

particle sizing

Ulf Willn, Global Sales Manager

Laser Diffraction & Imaging
Email: ulf.willen@malvern.com
Why measure particle size?

Develop better products

Speed up Time-to-Market
Improve product performance & quality
Reduce costs
Reduce customer rejection rates
Stay ahead of competition
Particle sizing: what needs to be considered?

it must be realised that

particle size analysis is not an
objective in itself but is a
means to an end, the end
being the correlation of
powder properties with some
process of manufacture,
usage or preparation.
Professor Harold Heywood (1905-1971)

H Heywood Proc. 1st Particle Size Anal. Conf. September 1966 p 355 - 359 (Heffer)
Particle sizing: what are we trying to predict?

Size measurements may predict:

Dissolution rate
Flowability (of a powder)
Viscosity (of a suspension)
Reaction Rate
Stability
Texture / Mouth feel
Uniformity
Packing density
Color and appearance
Inhalation risk
Concepts

You are given a regular-shaped object and asked to

give a one-number indication of its size.
What would your reply be ?
Concepts

It is not possible to describe the 3-dimensional object

with a single number!

360 m

140 m

120 m
Concepts: Equivalent spheres

The rectangular has the same volume as a sphere of

226um diameter (volume equivalent)

360 m

140 m

120 m
226 um
226
Concepts: Equivalent spheres
Sample preparation
Sample preparation: what do we need to
consider?

Dr. Henk Merkus Quality Assurance in Particle Size Measurement from

Improving Standards in Particle Size Distribution Measurement, February 17-
19, 1997, at the Engineering Research Centre for Particle Science and
Technology
Sampling

=
How much sample do I need to measure?

A representative result requires a certain

number of particles to be measured
For example 9

and the bigger the particles

the bigger the mass
The amount of material required to achieve good
sampling increases as the particle size increases
Sampling: particle segregation
Sampling: using a spinning riffler

Sample stream Sample pots on a

from a vibrating revolving tray
hopper
Sampling: obtaining unbiased samples from
slurry systems

Stirrer

Isokinetic sampling
probe

Speed of sample rise

matches sample
extraction velocity
Flow baffles
What should be the goal of the dispersion?
The particle size of agglomerates will affect sedimentation
rates.
The primary particle size of an active ingredient for a
tablet blend will influence its dissolution and bioavailability
Liquid dispersion
Dispersing particles in liquids requires the
following steps to be followed

Chose an appropriate dispersant

Ensure the correct concentration is used
Determine how energy input changes the
measured particle size
Confirm results using a referee technique
Sample preparation: what do we need to
consider?
Wet dispersion

Initial Dispersion (Pump and Stirrer) Ultrasound Applied Ultrasound Off

250

Dv10
Particle Size / Microns

200 Dv50
Dv90

150

100

50

0 5 10 15 20
Measurement Number
Method Validation Pre-sonication

After inappropriate level of sonication broken particles

With reduced level of sonication no broken particles

Dry dispersion
Dispersing particles dry requires the following
steps to be followed

Ensure the correct concentration is used

Determine how energy input changes the
measured particle size
Confirm results using a referee technique
Dry Powder Dispersion

Dry powder dispersion mechanisms

Energy input
Sample preparation: changes in size as a
function of pressure
A Pressure/particle-size titration should in the ideal case identify
a region where particle size is nearly constant over a range of
pressures, indicating that agglomerate dispersion has occurred
without particle breakup (ISO 13320:2009)
600
Dv10
Dv50
500 Dv90

400
Size / m

300

200

100

0
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0

Pressure / bar
Presenting the data
Number and volume based distributions

n% v%
100 50
Number and volume based distributions

n% v%
100 50
Number and volume based distributions

n% v%
100 50
Distribution statistics

Specifications are seldom based on the entire

distribution, but instead normally consider specific
distribution parameters or statistics.
Choosing the most relevant parameter and making a
judgment as to whether a single figure is adequate
or whether multiple descriptors of distribution are
important steps in the specification setting process
Distribution statistics

Median
The value of the particle size which
divides population into two equal halves
MMD, D50, D(n,0.5), D(v,0.5)
Mean
Arithmetic average of the data
D(1,0), D(3,2), D(4,3) etc.
Mode
The highest point of the frequency distribution
Setting specifications: distribution statistics

Median

Dv90 Sample Sample

D10 Dv50
D50 D90
(m) (m) (m)
A A 0.55 2.10 5.55

B B 0.29 2.10 15.40

D50

D10
Distribution statistics

Mean
There are many different means that can be defined
depending upon how the distribution data are collected and
analyzed. The three most commonly used for particle sizing
are:

Number length mean D[1,0] or Xnl

Surface area moment mean D[3, 2] or Xsv

Volume moment mean D[4, 3] or Xvm

Distribution statistics

Consider a particle population consisting of one million

1m particles and one with a diameter of 100 m.

1,0 1m 3,2 2m 4,3 50.5m

If we add one 150m particle then:

1,0 1m 3,2 5.2m 4,3 112m

3 4
1,0 3,2 4,3
2 3
Distribution statistics

Median Mode
% Volume

49% 51%

Dv10 D[3,2] Dv50 D[4,3] Dv90 Diameter

Summary

Need to consider sampling and sample

dispersion
The mean is an average particle size. There is
no unique mean
We can average all particle diameters, weighting
them according to their volumes, surface areas,
numbers or any other physical characteristic
Each mean will show different sensitivities to
changes in the distribution