Selecting the Best Particle Size Analyzer for your Application

© 2010 HORIBA, Ltd. All rights reserved.

Finding the Best Particle Characterization Analyzer for your Application

Mark [email protected]


First Questions

Why is the measurement being made?How will the data be used?Need to match historic data? Is particle size only enough information? Shape, zeta potential, mW

Who will use the instrument?R&D, QC, students, “the third shift”?

How many samples per day/week/month?


Is it a Particle Size Problem*?

Technical Problem

Yes No

No

Use Appropriate Characterization

Technique

Try otherAnalyticalTechniques

Is it a particle characterization issue?

Yes

Is it a material characterization issue?

*From Pohl, M., Choosing the rightParticle size analyzer, Powder andBulk Engineering, Feb 2008


Is it a Particle Size Problem*?

Customers complain this batch doesn’t perform like previous product Investigate specific behavior & look for possible

causesChemical or physical difference?

I have a powder flow problemBoth particle size & shape influence flowBut so do other parameters (water content)

This product isn’t stableCould be size and/or zeta potentialCause could come from surface chemistry


Choosing the Technique

Yes

Particle Size

Surface Area

Zeta Potential

Porosi-metry

Other Techniques

Which technique is most appropriate?

What arepossible

approaches?

Other Techniques

Is it a particle characterization issue?

ParticleCounting?

Contamination?Filtered?Need conc.?

From Pohl, M., Choosing the rightParticle size analyzer, Powder andBulk Engineering, Feb 2008

Particle size distribution is mostcommon problem/interest


Particle Counting

Need to know particles/volumeImplies measuring contamination,

typically in a filtered fluidParticle size analyzers measure your

product, not contaminationAir: use airborne particle counterLiquid: use liquid particle counter or trap

particles on filter and inspect filter– Coulter counter, light obscuration, some dynamic image analyzers


Electrical Sensing Zone

Coulter PrincipleBased on change in

conductivity of aperture as particle traverses.

Requires conducting liquid.Directly measures particle

volume and counts.High resolutionUsed for blood cell counting

now more than industrial applications


Light Obscuration:

Need to know concentration Filtered liquids Particles/ml @ size

Light Obscuration

Light Source

Liquid Flow

Sensing Zone

DetectorLight is blocked by single particles as they traverse the light beam

Particles in water, oil USP<788> testing High resolution histogram


USP<788> Filter Testing

Load Sample(s)

PSA300 Image Analyzer Scan Filter Count/Size all Particles


USP<788> Filter Testing

Mosaic function stitches all scansComplete fiber is analyzed

Generate Report


Particles or Water in Oil

Flow chambers50um – 1mm 2mm-6 mm


Droplets vs. Particles

Distinguishing between two would be easy if they looked like this

Droplets Particles


Droplets vs. Particles

Agglomerated droplets Sand


Pattern Matching Algorithm

User selects examples of droplets, iron sulfide, sand particles

Software looks at many size/shape values

Chooses how to discriminate

Bins each particle by type, counts

Can calculate ppmtime

ppm


Surface Area

If surface area influences product performanceSA-9600: 0.1-2000 m2/gBET Multi or single pointQuick, easy to use


Particle Sizing Possible Techniques

Direct Observation

Ensemble Averaging

Individual Particle

Counting

Indirect Observation

Possible Techniques

Optical Microscope STEM AFM

Static Image Analysis

Dynamic Image Analysis

PossibleTechniques

Sedimentation

StaticLight

Scattering

DynamicLight

Scattering

AcousticSpectroscopy

Possible Techniques

ElectricalConductivity

Single ParticleOptical

Spectroscopy

Light ScatteringNon-Orifice

PossibleTechniques

FisherSub-sieve

Size

HegmanGrindGauge

BlainePermeameter

ManyOthers

What are possible techniques?


Possible Criteria Effecting the Selection

Type of data desired Sample particle size range Sample concentration Sample behavior Sample type Industry acceptability


Type of Data Desired

Particle size (average) Particle Size distribution (D10, D50,

D90) Particle zeta potential Particle shape Surface area


Sample Type

Dry powder, suspension, emulsion, aerosol Size range, upper & lower limit Sample chemistry Particle shape Previous analysis technique


Sample Behavior

Is the typical sample stable? Is the sample stable at elevated or

reduced temperatures? Can the sample be diluted without

changing the particle size? Is the sample stable following dilution? Does the sample adhere to glass, plastic,

metal, etc.?


Industry Acceptability

Is there an ASTM or ISO Standard already in place?

Is there a trade association standard? Is there a supplier or end-user

specification? Does it meet company standards? Is the technique consistent with a QA

procedure development


Size Range by Technique

•MICROSCOPY

•ELECTROFORMED MESH •SIEVES

•CENTRIFUGAL SEDIMENTATION

•ELECTRICAL CONDUCTIVITY

•DYNAMIC LIGHT SCATTERING

•PERMEABILITY

•LIGHT OBSCURATION

•STATIC LIGHT SCATTERING

0.01µ 0.1µ 1µ 10µ 100µ 1000µ


Size Range by HORIBA Technique


From PQRI Group*

*PQRI Recommendations on Particle-Size Analysis of Drug Substances Used in Oral Dosage FormsJOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 96, NO. 6, JUNE 2007


Sieves

Weight % sample caught on known screen sizes Solid particles 20 m – 125 mm Low equipment costDirect measurement method Some automation/calculation available

More information available through www.retsch.com


Sedimentation

Stokes Law

Time

Sedimentation of same density material in a viscous medium

D = 18 µ Vp

(A - B) G

Vp = Settling velocity of discrete particleG = Gravity constantA = Density of ParticleB = Density of Carrier FluidD = Diameter of discrete particleµ = Viscosity of Carrier Fluid

Disc centrifuge


Manual Microscopy Inspect particles in a given

field of viewRepeat process for a

number of fieldsUse graticule to obtain sizeGet size, shape sometimes

count informationReferee technique: direct

Advantages:SimpleInexpensiveCan see shape

Disadvantages:SlowMeasures very few particlesVery tedious


Need Shape Information?Two Image Analysis Approaches:

Dynamic:particles flow past camera

Static:particles fixed on slide,stage moves slide


Basic Operations

Image Acquisitionand enhancement

Thresholding

Image Processing

Measurements

Objective &camera

Subjective orautomatic

Decisions orblack box

Focus, take picture

Separate particles from background

Edge definition, fill particles,Separate touching particles

Create size & shape distributions


Static Image Analysis: PSA300

Load slide onto automated stageMove slide, stop, take image, repeatHigher magnification = smaller particles

Sample preparationdevice necessary*to disperse powdersonto slide(s).Load powder into nozzle,pull vacuum, release.

*unless large free flowing powder


Static Image Analysis Applications

Powders, suspensions 0.5 – 1000 µmSize and shape informationAlso count when analyzing filters

API’s Excipients Lotions Aerosols Filters

Widely used in pharmaceutical R&DBut also wherever shape info. required

Abrasives


Dynamic Image Analysis: CAMSIZER

Size and shape from 30 µm – 30 mm

Particles fall from vibratingtray through inspectionzone. Two camerastake images ofparticles

Analyze imagesSize and shapedistributions


Replace Sieve Analysis

Similar size range, Xcmin matches sieve results, quick + shape


Dynamic Image Analysis Applications

Powders 30 µm – 30 mmGlass beads Sugar spheres Fertilizers Catalysts

Coating thickness

x [mm]1.4 1.6 1.8 2.0 2.2 2.4 2.6 2.80

10

20

30

40

50

60

70

80

90

Q3 [%]

0

20

40

60

80

100

120

140

160

180

q3 [%/mm]

CoMo2-0,1%Absch_xc_min_001.rdf

x1 x2


Need Widest Dynamic Range?

Laser Diffraction•Particle size 0.01 – 3000 µm•Converts scattered light to particle size distribution

•Quick, repeatable•Most common technique•Suspensions & powders


Need Widest Dynamic Range?

30 nm silica

q(%

)

Diameter(µm)

0

14

2

4

6

8

10

12

10.00 3000100.0 10000

100

10

20

30

40

50

60

70

80

90

Coffee Results

Suspension Powders


Sample Volume

10 ml 2mL 35 ml 200 ml

•Wide range of sample cells depending on application•High sensitivity keeps sample requirements at minimum•Automatic solvent fill


Small Sample Volume (MiniFlow)

Colloidal Silica (weak scatterer)Median (D50): 35 nmSample Amount: 132 mg

Magnesium StearateMedian (D50): 9.33 μmSample Amount: 0.165 mg

Bio-degradable PolymerMedian (D50): 114 μmSample Amount: 1.29 mg


Paste Cell

Unique to HORIBA


Dry Powders

Measure as dry powder using dry powder feederMeasure in natural stateQuick, easy, no clean upIncrease air pressure to aid dispersionMinimum size ~ 0.25 µm

Disperse powder in liquidLiquids reduce surface tension, add

surfactant, use ultrasound to aid dispersionLower detection limit (<30 nm)


Powder: Wet vs. Dry? POWDER DISPERSION PROCEDURES

Obtain Representative SAMPLE

Reactivity Check

Reactive in Water Not Reactive Reactive in Water,and Organic Liquids in Water Not Reactive in

Organic Solvents

Soluble? DRY Water Solubility? Organic Liquid Check ANALYSIS

Reactive Not Reactive, or

Insoluble Insoluble Soluble

Select Select DRY Distilled/D.I. Water Organic Liquid ANALYSIS

No Wettable? Select

Surfactant

Yes

Not Dispersed Dispersed Dispersion Check

Dispersed Ultrasonic Energy Dispersion Check WET SLURRY Treatment ANALYSIS

Not Dispersed

Select Different Surfactant


Dry Powder Feeder Reproducibility

Direct flow of powder down to cellAuto feedback controls feed rateConstant mass flow = robust results

Automatic ISO13320calculations


HORIBA Diffraction Systems

LA-950: 0.01-3000 µm wet or dryModular, range of samplers, advanced

software including Method Expert

LA-300: 0.1 – 600 µm wet onlySmaller, more portable, less expensive


Measuring at Process Concentration

Light scattering typically requires dilution Does PSD change with dilution? Concern when studying dispersion Some samples are better analyzed without

any alteration Implies no sample preparation Dispersion stability studies often include zeta

potential and other parametersSize, zeta potential, pH, conductivity, temp,

surfactant concentration, titration studies


Advantages: Can accommodate high

sample concentrations Also zeta potential, pH,

conductivity, conc.

Acoustic Spectroscopy

Applications: Emulsions &

suspensions Dispersion stability

with zeta potential

Pulsed electric field applied to sampleSound interacts with sampleAttenuation converted to size


Dispersion Stability

Want stable dispersion Either suspensions or

emulsions Suspensions sediment &

flocculate Emulsions phase

separate, creaming or coalescence

good

bad

good

bad


Zeta Potential

If surface has + charge, then - ions attracted to surface

+ ions attracted to – ions, builds electric double layer

Slipping plane: distance from particle surface where ions move with particle

ZP = potential (mV) at slipping plane


Piezo crystal Electrodes

A

ColloidVibrationCurrent

CVI C Pp m

md

msmp

smspomd K

K

)()(

Mobility..Dynamic

Zeta Potential Probe

Electroacoustics – Zeta Potential


Hardware Configurations

Size

Zeta

Conductivity

Titrationburettes


pH Titration of Rutile 7%vl & Alumina 4%vl

85 nm

300 nm

PSD unstable @ IEPaggregates form


DT-1201 System

Particle size analysis 5 nm – 1000 m High concentration ~2- 40 wt% Dispersion stability studiesUsed in formulation to study effect of surface

chemistry on product stability and performance Fantastic research tool or just

best option for particle size without dilution


Dynamic Light Scattering (DLS or PCS)

Most common technique for sub-micron sizingRange: 1 nm – 1 m*

* Density dependent, when does settling become prominent motion?

D6kTR H

Frequency-IntensityDistribution

Frequency Shifted Signal

Stokes-Einstein


Zeta potential Measurement

2sin2 ・・・ nE

U d

Mobility

)(23

kafU・

・ζ　

－＋

ν0 ν0+νd

UZeta potential


DLS Applications Particle size of suspension 1 nm – 1 mBoth ends extended depending on sample

Zeta potential of dilute suspensionsOnly suspensions, small particles

Molecular weight, second virial coefficient

Proteins Nanoparticles Biomolecules


Conclusions

One general purpose particle size analyzer: laser diffractionFlexible, quick, easy

Want additional shape information: image analysisStatic: 0.5-1000 µmDynamic: 30 µm – 30 mm

– Replace sieve analysis

All particles < 1 µm: DLS, acoustics


Conclusions

Measure without dilution: acoustic spectroscopy: 3 nm – 1000 µmSize, zeta potential, conductivity, micro-

rheologyTalk to our applications expertsHave samples run on system of interestIt’s rare for one application to be equally

suited to more than one instrument


Selection Table


Why Only One Method?

Good idea to have several techniques If > 1 µm use microscope for referenceSieves useful to confirm presence of

large particles or to remove particles too large for another techniqueBeware: Use a different technique = get

a different answer It is important to understand how

analysis methods differ in order to know how to compare data


Thank-you

Visit the website: www.horiba.com/us/particleProduct informationMany application notesPrevious webinars

Technology

Selecting the Best Particle Size Analyzer for your Application