particle sizing by laser diffraction
Post on 15-Oct-2021
3 Views
Preview:
TRANSCRIPT
© 2017 Malvern Instruments Limited
Particle Sizing by Laser DiffractionDr Anne Virden
Product technical specialist – diffraction and analytical imaging
anne.virden@malvern.com
© 2017 Malvern Instruments Limited
Overview
› Introduction to particle sizing
› Introduction to laser diffraction
› Smarter particle sizing Smarter method development
Data quality advice
› Method development Method development for dispersion in liquid
Method development for dispersion in air
› Choosing the right specifications Understanding the size distribution
› Optical properties and optical modes
© 2017 Malvern Instruments Limited
Introduction to particle characterisation
› What is a particle?
› A particle can be defined as:
› ‘a minute portion, piece, fragment, or amount of matter’
› Naturally occurring examples include: Sand, soil, clay, pollen, dust, smoke, fog
© 2017 Malvern Instruments Limited
Introduction to particle characterisation
› What is a particle?
› A particle can be defined as:
› ‘a minute portion, piece, fragment, or amount of matter’
› The particles that we measure are in:
Dry powders Suspensions Emulsions Sprays
© 2017 Malvern Instruments Limited
What can measuring particle size tell us?
› Predicting product performance Dissolution rate
Content uniformity
Mouth feel assessment
Stability
Viscosity (of a suspension)
Colour
Flowability (of a powder)
© 2017 Malvern Instruments Limited
Why is particle size important?
› Controlling production processes Blending
Milling
Dispersion
Tableting
© 2017 Malvern Instruments Limited
Particles come in many different shapes
(as well as sizes)
How do we describe the size of these particles?
© 2017 Malvern Instruments Limited
Basic concepts of particle sizing
› You are given a regular-shaped object and a ruler and asked
to give a one-number indication of its size What would your reply be ?
© 2017 Malvern Instruments Limited
Basic concepts of particle sizing
› You may reply: “360x140x120mm” Which might be correct but it is not one number.
It is not possible to describe the size of this 3-dimensional object with a single
number
© 2017 Malvern Instruments Limited
Concept of equivalent spherical diameters
› The rectangular box has the same volume as a sphere of
226µm diameter. The volume equivalent spherical diameter is 226μm
226μm
© 2017 Malvern Instruments Limited
How do we describe the size of a particle?
› Equivalent spheres Maximum length
Minimum length Max. length
Min. length
Max. lengthMin. length
© 2017 Malvern Instruments Limited
How do we describe the size of a particle?
› Equivalent spheres Maximum length
Minimum length
Sedimentation rate
Max. lengthMin. length
Sedimentation rate
Sedimentation rate
© 2017 Malvern Instruments Limited
How do we describe the size of a particle?
› Equivalent spheres Maximum length
Minimum length
Sedimentation rate
Sieve aperture
Max. length
Min. lengthSedimentation rate
Sieve aperture
Sieve aperture
© 2017 Malvern Instruments Limited
How do we describe the size of a particle?
› Equivalent spheres Maximum length
Minimum length
Sedimentation rate
Sieve aperture
Surface area
Max. length
Min. lengthSedimentation rate Sieve aperture
Surface area
Surface area
© 2017 Malvern Instruments Limited
How do we describe the size of a particle?
› Equivalent spheres Maximum length
Minimum length
Sedimentation rate
Sieve aperture
Surface area
Volume
Max. length
Min. lengthSedimentation rate Sieve aperture
Surface area
Volume
© 2017 Malvern Instruments Limited
Concept of equivalent spherical diameters
› Different particle sizing techniques report different
equivalent spherical diameters Dependent on the physical property that is measured
© 2017 Malvern Instruments Limited
Introduction to laser diffraction
© 2017 Malvern Instruments Limited
The basic principles of laser diffraction
› The diffraction pattern:
© 2017 Malvern Instruments Limited
Dependence of diffraction pattern on particle size
Large particle Small particles
Incident lightSmall angle scattering
Incident light Large angle
scattering
© 2017 Malvern Instruments Limited
Measuring the scattering pattern: Spraytec
Light source
Measurement zone
Data collection lens Detector system
Collimating
opticsAuto-align stage
Data acquisition
system
IP65 enclosures
© 2017 Malvern Instruments Limited
Measurement cell Focal plane
detectors
Side scatter
detectors
Back scatter
detectors
633nm red
laser
Precision
folded optics
Measuring the scattering data: Mastersizer 3000
© 2017 Malvern Instruments Limited
Measuring the scattering data: Mastersizer 3000
470nm blue
light source
Side scatter
detectors
Measurement cell
Back scatter
detectors
© 2017 Malvern Instruments Limited
The measured scattering data
Increasing angle / Decreasing particle size
Red light detectorsBlue light
detectors
Extinction detectors:
51 and 63
© 2017 Malvern Instruments Limited
Example data set: large particles
› Large particles scatter at low angles
› Scattering data is concentrated on low angle detectors With high intensity (light energy)
© 2017 Malvern Instruments Limited
Example data set: small particles
› Small particles scatter light at high angles
› Scattering data is concentrated on high number detectors With low intensity (light energy)
© 2017 Malvern Instruments Limited
Laser diffraction instrumentation
› Wide dynamic range ideal for polydisperse samples
› Wet, dry or spray measurements
› Ensemble method, good sampling
› Lab (Mastersizer, Spraytec) and process (Insitec) solutions
› Widely accepted and standardized
© 2017 Malvern Instruments Limited
Particle size measurement ranges
Particle size
Laser diffraction
0.1nm 1nm 10nm 100nm 1μm 10μm 100μm 1mm 10mm
Dynamic light scattering
Sedimentation
Electrozone sensing
Sieving
Nanoparticle tracking
Taylor dispersion analysis
Automated imaging
Spatial filter velocimetry
Resonant mass measurement
© 2017 Malvern Instruments Limited
Smarter particle sizing
© 2017 Malvern Instruments Limited
Introducing the Mastersizer 3000
› Extensive measurement capabilities 10nm to 3.5mm range
10kHz data acquisition
› Rapid and effective wet dispersion Efficient in-line sonication
› Cutting-edge dry dispersion Suitable for fragile and cohesive samples
› Software that eases your workload Direct measurement feedback
Method development guidance
Data quality assessment
Easy result reporting
© 2017 Malvern Instruments Limited
Laser diffraction measurement process
Sampling
Dispersion and stabilisation
Optical alignment
Background signal collection
Sample signal collection
Data analysis
Reporting and interpreting results
© 2017 Malvern Instruments Limited
When do sampling and dispersion matter?
Particle size
% E
rro
r
Instrumentation
Sampling
Dispersion
Sampling
© 2017 Malvern Instruments Limited
How much sample do I need to measure
› A certain number of particles must be measured in order to
obtain a representative result For larger particles a greater mass of sample must be measured to ensure sufficient
particles are measured
0.00
0.50
1.00
1.50
2.00
2.50
0 200 400 600 800 1000
Min
imu
m m
ass
/ g
Dv90 / μm
Sampling
© 2017 Malvern Instruments Limited
Data Quality: Ensure representative sampling
Sampling
© 2017 Malvern Instruments Limited
The Mastersizer 3000: Wet dispersion units
Hydro EV Hydro LV Hydro MV Hydro SM Hydro SV
Volume/mL 1000/600ml 600ml 120ml 50-120 6-7ml
Dispersion and stabilisation
© 2017 Malvern Instruments Limited
How do we disperse particles in liquid?
› Stirring and ultrasound are used to disperse agglomerates
1: Before ultrasound 2: During ultrasound 3: After ultrasound
Dispersion and stabilisation
© 2017 Malvern Instruments Limited
Direct feedback on measurement stability is provided
Dispersion and stabilisation
after ultrasound
© 2017 Malvern Instruments Limited
Smarter method development: SOP player
Dispersion and stabilisation
© 2017 Malvern Instruments Limited
Diagnosing stability problems
Dispersion and stabilisation
© 2017 Malvern Instruments Limited
Hydro Sight
› In-line imaging accessory allowing
users to view the dispersion
› Helps users to optimise and
troubleshoot their methods
© 2017 Malvern Instruments Limited
Hydro Sight
› Size range Measurement: 9 - 1000 µm
Observation: 1.4 - 1400 µm
› Measures size and elongation Also calculates the degree of sample dispersion
› Works with recirculating liquid
sample dispersion units: Hydro SM / EV / LV / MV
› Simple installation Connected between the dispersion unit and the
optical bench
© 2017 Malvern Instruments Limited
Hydro Sight aids method development by providing sample
images which show the state of dispersion
© 2017 Malvern Instruments Limited
Following dispersion trends using Hydro Sight
© 2017 Malvern Instruments Limited
The software can also be configured to automatically
detect sample anomalies
© 2017 Malvern Instruments Limited
Dry powder dispersion - Aero
› 0.1 mm to 3500 mm
› Precise pressure control 0.1 to 4.0 bar range
› Modular venturi disperser Standard suitable for most powders
Options for cohesive or abrasive samples
› Modular sample tray design Hopper unit for large sample quantities
Micro and Macro trays for smaller quantities
› Full software control
© 2017 Malvern Instruments Limited
Exchangeable dispersers enable the development
of a range of applications
Dispersion and stabilisation
Standard Venturi High-Energy Venturi
© 2017 Malvern Instruments Limited
Data Quality: Optical alignmentOptical alignment
© 2017 Malvern Instruments Limited
Data Quality: Background
› Background level and stability can be assessed before sample
addition Ensures confidence in measurement quality
Background signal collection
© 2017 Malvern Instruments Limited
Data Quality: How much sample should I add
Sample signal collection
© 2017 Malvern Instruments Limited
Data Quality: How much sample should I add
Sample signal collection
© 2017 Malvern Instruments Limited
Data Quality: Optical models and optical properties
› The data quality system provides advice on the choice of
optical model and optical properties
Data analysis
© 2017 Malvern Instruments Limited
Customise reports for your application
› Customise reports with Graphs
Tables
Parameters
Calculations (text, tables and graphs)
Signature tables
Pictures
Reporting and interpreting results
© 2017 Malvern Instruments Limited
Easily review results from multiple record files
Reporting and interpreting results
© 2017 Malvern Instruments Limited
Direct support is provided via the Malvern Portal
Reporting and interpreting results
© 2017 Malvern Instruments Limited
Choosing the right specificationsThe particle size distribution explained
© 2017 Malvern Instruments Limited
Understanding particle size results: Distribution type
› Type of distribution result depends on measurement
technique Number
Mass
Volume
Intensity
› Always set specifications using the type of result measured
by the system Transforming the result type greatly increases the potential error
© 2017 Malvern Instruments Limited
Particle size distribution statistics: Median and Mode
› Median = midpoint of the distribution
› Mode = most commonly occurring size class
Diameter
% V
olu
me
Gaussian Distribution
ModeMedian
%
© 2017 Malvern Instruments Limited
PSD Statistics: Median and Mode
› If the distribution shape is more complex then these
parameters will diverge
Diameter
% V
olu
me
Mode
Median
49% 51%
Bimodal Distribution
%
© 2017 Malvern Instruments Limited
PSD Statistics: Percentiles
› Percentiles are the size below which there is a certain
volume of the sample Taken from the cumulative distribution
Diameter
% V
olu
me
Diameter
% V
olu
me
Cu
mm
ula
tive
dis
trib
uti
on
/ %
0
10
20
30
40
50
60
70
80
90
100
Dx10 Dx50 Dx90
© 2017 Malvern Instruments Limited
PSD Statistics: Mean particle sizes
› The most familiar mean is the arithmetic mean
𝑋𝑛𝑙 = 𝐷 1,0 =11 + 21 + 31
10 + 20 + 30=1 + 2 + 3
3= 2
› Different particle sizing techniques report different mean
sizes, depending on the sensitivity of the technique Image analysis reports a number weighted mean
• D[1,0]
Laser diffraction reports the volume weighted mean
• D[4,3]
• And surface area weighted mean, D[3,2]
© 2017 Malvern Instruments Limited
PSD Statistics: Volume weighted mean
› D[4,3] is sensitive to changes in the coarse particle fraction Useful for monitoring milling or dispersion
D[4,3] = 11.2
D[4,3] =7.95
© 2017 Malvern Instruments Limited
PSD Statistics: Surface area weighted mean
› D[3,2] is sensitive to changes in the fine particle fraction Useful when surface area is important
D[3,2] = 34.4μmD[3,2] = 59.1
© 2017 Malvern Instruments Limited
Diameter
% V
olu
me
Particle size distribution statistics: Summary
› Percentiles
› Averages, weighted by number, surface area or volume
› Avoid parameters with high variability, such as Dx100
Dx10 Dx50 Dx90D[3,2] D[4,3]
Dx100%
D[1,0]
© 2017 Malvern Instruments Limited
Choosing the right parameter to follow the process
› Blend of coarse and fine particles
0
10
20
30
40
50
60
70
80
90
100
0.1 1 10 100 1000 10000
Cu
mu
lati
ve v
olu
me %
Size / um
coarse
1% fines
5% fines
10% fines
20% fines
30% fines
fines
© 2017 Malvern Instruments Limited
Choosing the right parameter to follow the process
› Choose the parameter that shows the greatest sensitivity in
the region of interest
0
50
100
150
200
250
300
0 20 40 60 80 100
Siz
e /
um
Fines /%
Dv10
D[3,2]
Dv50
D[4,3]
Dv90
© 2017 Malvern Instruments Limited
Example: Factors affecting the tableting process
› Particle size Smaller particle size increases particle adhesion
Greater adhesion can lead to voiding, cracking and breakage
Affects flowability of powder into the die
› Particle size distribution Close overlap between actives, excipients and binders is ideal
Narrow distributions improve content uniformity
Wider distributions increase packing density
© 2017 Malvern Instruments Limited
Example: Tablet formulation
© 2017 Malvern Instruments Limited
Example: Tablet formulation
Evolutions in Direct Compression, Douglas McCormick, Pharmaceutical Technology, April 2005. Pg 52-62
Parameter Target value
(μm)
Size specification
(μm)
Dv10 >30 40 ± 20%
Manufacturing spec 32 to 48
D[4,3] >80 110 ± 20%
Manufacturing spec 88 to 132
Dv90 <1000 200 ± 20%
Manufacturing spec 160 to 240
© 2017 Malvern Instruments Limited
What precision values are reasonable?
› ISO13320-1: Section 6.4 Dv50 - 5 different readings: COV < 3%
Dv10 and Dv90: COV < 5%
“Below 10μm, these maximum values should be doubled.”
› In ideal conditions 0.5% COV on parameters >1μm
1% COV on parameters <1μm
› USP <429> and EP 2.9.31 Provides reproducibility ranges
Dv50 or any central value: <10%
Dv10, Dv90 or any non-central value: <15%
“Below 10μm, these maximum values should be doubled.”
© 2017 Malvern Instruments Limited
Example: Tablet formulation
› Specifications should be tightened to account for analytical
variation Ensures that the manufactured material is in specification
› Using the USP guidance for reproducibility 10% on central values
15% at distribution edgesParameter Target value (μm) Size specification (μm)
Dv10 >30 40 ± 20%
Manufacturing spec 32 to 48
(narrow specification by 15%) Measurement limits 36.8 to 40.8
D[4,3] >80 110 ± 20%
Manufacturing spec 88 to 132
(narrow specification by 10%) Measurement limits 96.8 to 118.8
Dv90 <1000 200 ± 20%
Manufacturing spec 160 to 240
(narrow specification by 15%) Measurement limits 184 to 204
© 2017 Malvern Instruments Limited
Linking measurement data and manufacturing
specifications
How to Establish Manufacturing Specifications, Donald J. Wheeler, Statistical Process Controls Inc.
Posted on spcpress.com May 2003
Particle Size
Product Specification
Measurement Specification
Upper Product
Acceptance Limit
Lower Product
Acceptance Limit
Lower Measurement Limit Upper Measurement
Limit
ss
© 2017 Malvern Instruments Limited
Method development for dispersion in liquids
© 2017 Malvern Instruments Limited
The purpose of method development
› A laser diffraction measurement requires
‘a representative sample, dispersed at an adequate concentration in a suitable liquid
or gas’
<USP429>
› Method development must define appropriate Sampling
Dispersion
Measurement conditions
© 2017 Malvern Instruments Limited
Is sampling or dispersion more important?
› The greatest source of error in particle size measurements
depends on particle size Dispersion is most important for fine particles
Sampling is most important for coarse particles
Choice of dispersant
Sonication
(dispersion energy)
Sampling
Sampling
Measurement time
Dispersant
Fine particlesCoarse particles
© 2017 Malvern Instruments Limited
What happens to particles during transportation
› Particle can segregate during transit This can lead to sampling bias
Courtesy of A.J. Morris, M. Glover and M. Probert
© 2017 Malvern Instruments Limited
What happens to particles during transportation
› Particle can segregate during transit This can lead to sampling bias
Courtesy of A.J. Morris, M. Glover and M. Probert
© 2017 Malvern Instruments Limited
Measuring in the appropriate state of dispersion
Agglomerated Dispersed
© 2017 Malvern Instruments Limited
The liquid dispersion process
Wetting the sample
Choose an appropriate dispersant
Carry out a beaker test
Use surfactant to improve the dispersion
Adding energy to improve dispersion
Stirring/pumping by the dispersion unit
Application of ultrasound
Stabilising the dispersion
Check repeatability after ultrasound
Additives can be used to prevent re-agglomeration
© 2017 Malvern Instruments Limited
Wetting the sample
Dispersant
Water/DI water
Organic acids
Alcohols(methanol / ethanol / isopropyl alcohol)
Simple alkanes(hexane / heptane/ iso-octane / cyclohexane)
Long-chain alkanes and alkenes(dodecane / mineral oils / sunflower oils / palm oil)
Po
larity
Dispersant requirements
Sample wetting
Not dissolve the sample
Bubble free
Suitable viscosity
Transparent to the laser beam
Different refractive index to the sample
Chemically compatible with the instrument
Choose an appropriate dispersant
Carry out a beaker test
Use surfactants to improve
wetting
© 2017 Malvern Instruments Limited
Wetting the sample
Choose an appropriate dispersant
Carry out a beaker test
Use surfactants to improve
wetting
Stabilization Examples
Steric Igepal CA-360, Tween 20/80, Span
20/80
Electrosteric Anionic: SDS (sodium dodecylfulfate),
AOT (sodium-bis-2-
etheylhexylsulfosuccinate)
Cationic: CTAB (cetyltimethlammonium
bromide)
DI water DI water + surfactant
© 2017 Malvern Instruments Limited
Adding energy to improve dispersion
0
10
20
30
40
50
60
70
80
90
100
0 2 4 6 8 10 12 14 16 18 20
Siz
e /
um
Measurement no.
Dx (10) (μm) Dx (50) (μm) Dx (90) (μm)
Stirring
© 2017 Malvern Instruments Limited
Adding energy to improve dispersion
0
10
20
30
40
50
60
70
80
90
100
0 2 4 6 8 10 12 14 16 18 20
Siz
e /
um
Measurement no.
Dx (10) (μm) Dx (50) (μm) Dx (90) (μm)
Ultrasound
© 2017 Malvern Instruments Limited
Adding energy to improve dispersion
0
10
20
30
40
50
60
70
80
90
100
0 2 4 6 8 10 12 14 16 18 20
Siz
e /
um
Measurement no.
Dx (10) (μm) Dx (50) (μm) Dx (90) (μm)
After
Ultrasound
© 2017 Malvern Instruments Limited
Identifying dispersion: obscuration
› Obscuration increases as agglomerates disperse
0
2
4
6
8
10
12
0 5 10 15 20 25 30
Ob
scu
rati
on
/ %
Measurement no.
Obscuration
Ultrasound on
Ultrasound off
© 2017 Malvern Instruments Limited
Dispersion trend: scattering data
› During dispersion, as the particles get smaller Scattering on inner detectors decreases
Peak shifts to higher angle detectors
Trend across repeat measurements
Loss of scattering on inner detectors
Reminder: detector number increases with angleScattering from larger particles falls on low angle detectors
© 2017 Malvern Instruments Limited
Dispersion trend: Particle size distribution
› Overlay the results of an ultrasound titration Should show gradual dispersion
Agglomerates dispersing
© 2017 Malvern Instruments Limited
Without
ultrasound
With
ultrasound
The dispersion process: Verification
© 2017 Malvern Instruments Limited
Stabilising the dispersion
0
10
20
30
40
50
60
70
80
90
100
0 2 4 6 8 10 12 14 16 18 20
Siz
e /
um
Measurement no.
Dx (10) (μm) Dx (50) (μm) Dx (90) (μm)
© 2017 Malvern Instruments Limited
Stabilising the dispersion
0
10
20
30
40
50
60
70
80
90
100
0 2 4 6 8 10 12 14 16 18 20
Siz
e /
um
Measurement no.
Dx (10) (μm) Dx (50) (μm) Dx (90) (μm)
Admixtures – increase particle charge
• e.g. Sodium hexametaphosphate,
sodium pyrophosphate, Ammonium
citrate
• pH can also be important• ‘The use of zeta potential measurements for
improving dispersion during particle size
determination’ (MRK373)
© 2017 Malvern Instruments Limited
How stable should the results be?
› ISO13320-1: Section 6.4
Dv50 - 5 different readings: COV < 3%
Dv10 and Dv90: COV < 5%
“Below 10μm, these maximum values should be doubled.”
› In ideal conditions
0.5% COV on parameters >1μm
1% COV on parameters <1μm
© 2017 Malvern Instruments Limited
Checking the stability of the results
› The live trend shows the variability of the results RSDs should be within ISO limits
13.3μmAv RSD13.3 0.465%
Av RSD7.32 0.11%
Av RSD3.77 0.0357%
7.32μm
3.77μm
© 2017 Malvern Instruments Limited
How do measurement conditions affect results?
› Appropriate amount of sample Good signal to noise ratio
Avoid multiple scattering
› Correct stir speed Fast enough to prevent sedimentation for large/dense particles
Slow enough not to break emulsions
› Correct measurement duration Long enough to sample all of the particles in the dispersion unit
© 2017 Malvern Instruments Limited
What defines the low obscuration limit?
› Signal to noise ratio Large particles scatter a lot of light
Even at low obscuration's there will be a lot of sample data (relative to the
background and noise)Scattering from ~40 micron glass
beads, at 7% obscuration, produces ~250 units of light energy
- significantly higher than the background
© 2017 Malvern Instruments Limited
What defines the low obscuration limit?
› Signal to noise ratio Small particle scatter light more weakly
It is important to make sure that the background is stable before measuring fine
particles
Scattering from 2 micron latex, at 5% obscuration produces ~8 units of light energy – still sufficiently higher than
the background
© 2017 Malvern Instruments Limited
What defines the low obscuration limit?
› The reproducibility of the measurement may also define the
low obscuration limit Particularly if the particle size is large and the distribution is broad
› You can test this by measuring several sub samples of your
material If the results are within acceptable variation then the obscuration is sufficient
Measurements with high variability may be improved by measuring at higher
obscuration (more sample)
© 2017 Malvern Instruments Limited
What defines the upper obscuration limit?
› If we add too much sample the results may be affected by
multiple scattering This generally affects samples smaller than 10μm
Measurement cell
Dete
cto
r
Low angle
detectors
High
angle
detectors
© 2017 Malvern Instruments Limited
What defines the upper obscuration limit?
› If we add too much sample the results may be affected by
multiple scattering This generally affects samples smaller than 10μm
Measurement cell
Dete
cto
r
Low angle
detectors
High
angle
detectors
Increase in
scattering angle
© 2017 Malvern Instruments Limited
How does multiple scattering affect the results
› This can be tested by measuring at increasing obscuration
› For this 1μm sample results at obscurations of 9% and
above show a reduction in size due to multiple scattering
Obscuration (%) Dv (10) (μm)
5.3 0.38
7.04 0.37
9.17 0.34
14.78 0.27
18.81 0.20
© 2017 Malvern Instruments Limited
Target obscuration ranges: Wet measurements
Particle size range Example Obscuration
Very fineVery low obscurations are used to avoid
multiple scattering
<5%
FineLow obscurations are used to avoid multiple
scattering
5% to 10%
CoarseHigher obscurations are used to improve
sampling
10% to 20%
Very polydisperseHigher obscurations are used to improve
sampling- test with multiple sub samples
10% to 20%
© 2017 Malvern Instruments Limited
Determine the correct stir speed
› For coarse or dense materials particle size will increase with
stir speed until all particles are suspended A stable particle size is obtained above 2500rpm
0
20
40
60
80
100
120
140
160
180
500 1000 1500 2000 2500 3000 3500
Pa
rtic
le s
ize
/ μ
m
Stir speed / rpm
d10 dv50 d90
© 2017 Malvern Instruments Limited
Determine the correct measurement duration
› For broad distributions measurement duration must be
sufficient to sample all particles in the system.
© 2017 Malvern Instruments Limited
Affect of measurement duration on variability
› Result variability is reduced as measurement duration is
increased Variability is within ISO limits when duration ≥10s
0
1
2
3
4
5
6
7
8
0 5 10 15 20 25
% R
SD
(D
v50)
Measurement duration / s
© 2017 Malvern Instruments Limited
Summary of wet method development
› Dispersion Choice of dispersant
Adding energy to disperse agglomerates
Stabilising the dispersion
Verifying the state of dispersion
› Measurement conditions Sample concentration – obscuration
Stirrer speed – particle suspension/shearing
Measurement duration
© 2017 Malvern Instruments Limited
Method development for dry dispersion
© 2017 Malvern Instruments Limited
When is dispersion important
› The greatest source of error in particle size measurements
depends on particle size Dispersion is most important for fine particles
Sampling is most important for coarse particles
Air pressure
Feed rate
Sampling
Fine particlesCoarse particles
Sampling
Air pressure
Feed rate
© 2017 Malvern Instruments Limited
Dry powder dispersion: Mechanisms
› Importance of each mechanism depends on: Disperser geometry
Flow rate or air pressure
Material type
› Higher impact energies may improve the dispersion
effectiveness Needs to be balanced against the risk of particle break-up
Energy/aggression
© 2017 Malvern Instruments Limited
Dry powder dispersion: Disperser design
› Standard disperser Straight through design
No direct wall impaction
Suitable for most types of sample
› High energy disperser Elbow design
Direct impaction surface
Suitable for robust aggregated samples
© 2017 Malvern Instruments Limited
Ob
scu
rati
on
Time
Ta
rget
ra
ng
e
Step 1: Setting the feed rate
› Keep the obscuration in range during the measurement
© 2017 Malvern Instruments Limited
Dry powder dispersion: ISO guidance
› Degree of dispersion is controlled by primary air pressure Monitor change in size distribution with pressure
• Carry out pressure titration – Step 2
› Check that particle breakup has not occurred Compare dry results to a well dispersed wet measurement – Step 3
Choose the pressure which agrees with the wet results
• Shows dispersion and not particle breakage
Dry dispersion steps:
Step 1: Set up feed rate
Step 2: Measure pressure titration
Step 3: Compare to reference result
© 2017 Malvern Instruments Limited
Step 2: Measure a pressure titration
› Make measurements at 4, 3, 2, 1, 0.5 and 0.1 bar.
› Make repeat measurement at each pressure to check for
sample segregation
© 2017 Malvern Instruments Limited
Step 3: Compare dry results to wet
› Low pressure dry result shows larger result Indicates sample is not fully dispersed
© 2017 Malvern Instruments Limited
Step 3: Compare dry results to wet
› High pressure shows good agreement Suggests the material is dispersed
© 2017 Malvern Instruments Limited
Optional Step 4: High energy venturi
› For robust, highly agglomerated materials the high energy
venturi may be required.
Low pressure
High pressure
© 2017 Malvern Instruments Limited
Comparing standard and high energy venturis
40
50
60
70
80
90
100
110
120
130
140
0 0.5 1 1.5 2 2.5 3 3.5 4
Dv50 /
um
Air Pressure / bar
Aero Standard Aero High Energy Wet Dispersion
© 2017 Malvern Instruments Limited
Segregation in dry measurements
› Segregation can occur with free-flowing powders with wide
particle size distributions Characterized by a decrease in size over repeat measurements
Make several quick repeat measurements at each pressure
This can be done as part of the pressure titration
© 2017 Malvern Instruments Limited
Segregation in dry measurements
› Segregation can occur with free-flowing powders with wide
particle size distributions Characterized by a decrease in size over repeat measurements
Make several quick repeat measurements at each pressure
This can be done as part of the pressure titration
› Always measure the whole sample, either by: Making enough short measurements to use the whole sample and then create an
average
Make one long measurement long enough to use up all of the sample.
© 2017 Malvern Instruments Limited
Summary of dry method development
› Dispersion mechanisms
› Measurements conditions Feed rate
› Pressure titration Comparison to well dispersed wet measurement
› Segregation
© 2017 Malvern Instruments Limited
Optical properties and optical models
© 2017 Malvern Instruments Limited
What does laser diffraction measure?
› Laser diffraction systems measure the scattering pattern
produced by an ensemble of particles suspended in a laser
beam
© 2017 Malvern Instruments Limited
What does an optical model do?
› An optical model predicts the scattering pattern produced by
a particle
© 2017 Malvern Instruments Limited
What does an optical model do?
› And can predict the scattering pattern produced by many
particles
Size classes / m
0.01 0.1 1 10 100 1000 10000
Vo
lum
e d
en
sity
/ %
0
2
4
6
8
10
© 2017 Malvern Instruments Limited
How do we use the optical model?
› The Mastersizer measures scattered light energy vs angle
for samples of unknown size distribution
› An optical model can predict the scattering pattern
(scattered light energy vs angle) given a known particle size
distribution
› To obtain a particle size distribution from an unknown
sample we must use the optical model as part of a iterative
process…
© 2017 Malvern Instruments Limited
Use opticalmodel
How do we use the optical model?
© 2017 Malvern Instruments Limited
Scattering models: Mie Theory
› Models the interaction of light with matter Assuming that the particles are spherical
Assuming that it is a two phase system
› Valid for all wavelengths of light and all particle sizes
› Predicts the dependence of scattering intensity on particle
size
› Predicts that secondary scattering is observed for small
particles
‘For particles smaller than about 50μm Mie theory offers the best general solution’
ISO13320
© 2017 Malvern Instruments Limited
Mie Theory: Predicted scattering
Refracted light
© 2017 Malvern Instruments Limited
Mie Theory: Optical properties
Absorption
“….. the Mie theory offers the best
general solution.”
ISO 13320: 2009
© 2017 Malvern Instruments Limited
Scattering models: Fraunhofer approximation
› Basic assumption are similar to Mie Theory Assumes the particles are disc shaped
Assumes it is a two phase system
› Plus the additional assumptions that The refractive index difference is high (RRI > 1.3)
The particles are opaque
The wavelength of light is much smaller than the particle size
The angle of the scattered light is small
› In the Mastersizer 3000 software the Fraunhofer approximation is
available as a particle type
‘The advantage of this equation is that it is relatively simple and quick to calculate
‘This Fraunhofer approximation does not make use of any knowledge of the optical
properties of the material’
ISO13320
© 2017 Malvern Instruments Limited
Scattering models: Fraunhofer approximation
© 2017 Malvern Instruments Limited
Comparing the results of the scattering models
‘If the Fraunhofer approximation is applied for samples containing an
appreciable amount of small, transparent particles, a significantly
larger amount of small particles may be calculated.’
ISO13320
Mie TheoryFraunhofer Approximation
© 2017 Malvern Instruments Limited
Mie vs Fraunhofer: Data quality advice
© 2017 Malvern Instruments Limited
Mie vs Fraunhofer: Data Quality advice
© 2017 Malvern Instruments Limited
Which optical properties do we need?
› To use Mie theory correctly we need to know three optical
properties The refractive index of the dispersant
The refractive index of the sample material
The absorption of the sample material
• Also called the imaginary part of the refractive index
‘Good understanding of the influence of the complex refractive index in the light scattering
from particles is strongly advised in order to apply the Mie theory or the Fraunhofer
approximation appropriately.’
ISO13320
© 2017 Malvern Instruments Limited
The absorption (or imaginary refractive index)
› The absorption can be determined by looking at the
dispersed sample under a microscope and observing its Shape
Transparency
Internal structure
› Absorption is generally required to a factor of 10 E.g. 0.1 or 0.01 (not 0.023)
Images of some calcium carbonate
particles, an absorption of 0.01 would be
used for these particles, due to the
observed transparency of the particles.
© 2017 Malvern Instruments Limited
Estimating absorption from particle appearance
0
0.001
0.01
0.1
1.0+
Latices
Emulsions
Slightly colored powders
Crystalline milled powders
Highly colored
(complementary) and metal
powders
Appearance Absorption Example
© 2017 Malvern Instruments Limited
Methods for determining the refractive index
› Four main routes to refractive index information
References
ISO 13320 appendix
Malvern material database
CRC handbook
Manufacturers label (dispersant)
Online (luxpop, webelements,
google scholar)
Microscope observations
Empirical/semi-empiricalRefractometer measurements
© 2017 Malvern Instruments Limited
Choosing the refractive index
› A Refractive Index is generally only required to 2 decimal
places e.g. 1.42 not 1.4234
And to an accuracy of ±0.02
› Can be estimated based on similar materialsRefractive index
1 2 31.5 2.5
Plastics and elastomers (1.38 – 1.57)
Inorganic salts (1.52 – 1.8)
Organic compounds (1.4 – 1.7)
Metal Oxides (1.6 – 2.5)
© 2017 Malvern Instruments Limited
Assessing the data fit
› The fit report shows the measured and calculated scattering
data
› How well these overlay is known as the data fit
› The residual quantifies how good the fit is Residual = area between the two curves
Residual = 0.83%
© 2017 Malvern Instruments Limited
Inspecting the data fit: refractive index
› A poor fit to the focal plane or side-scatter detectors
suggests an incorrect choice of refractive index
Poor fit indicates incorrect choice of
refractive index
© 2017 Malvern Instruments Limited
Inspecting the data fit: absorption index
› Misfits to the extinction detectors indicate an incorrect
absorption value 51 in the red light
63 in the blue light
Poor data fit here indicates poor choice of absorption
Poor data fit here indicates poor choice of absorption
© 2017 Malvern Instruments Limited
Example - weighted
Example - unweighted
Weighted and un-weighted data fits
© 2017 Malvern Instruments Limited
Assessing the data fit: Example
› The user is seeing an “unexpected” mode of small material.
› The optical properties used were: RI:1.4, Absorption: 0.01
© 2017 Malvern Instruments Limited
Assessing the fit using 1.4/0.01
Weighted fit Weighted Residual = 3.26
Poor fit = incorrect RI
Un-Weighted fit Residual = 0.82
© 2017 Malvern Instruments Limited
Assessing the fit using 1.54/0.01
Weighted fit Weighted residual = 0.48
Un-Weighted fit Residual = 0.57 Improved fit
© 2017 Malvern Instruments Limited
Looking at the results
› Sample is calcium carbonate Reference RI is between 1.53 and 1.63
© 2017 Malvern Instruments Limited
The optical property optimiser (OPO)
› Offers a quick way to adjust optical properties and assess
the fit and result
© 2017 Malvern Instruments Limited
Overview
› Introduction to particle sizing
› Introduction to laser diffraction
› Smarter particle sizing Smarter method development
Data quality advice
› Method development Method development for dispersion in liquid
Method development for dispersion in air
› Choosing the right specifications Understanding the size distribution
› Optical properties and optical modes
top related