Modern Particle Characterization Techniques Image Analysis

Modern Particle Characterization
Techniques Series
Image Analysis
©2020, Innopharma Technology Ltd 1

Overview
Introduction
What is image analysis?
Common Questions
How Image Analysis is done
Future Perspectives
© 2020 HORIBA, Ltd. All rights reserved. 2

A word from our sponsor
Did you sign up for our newsletter?
Receive regular updates and news on the

world of particle analysis.
Send us a chat or e-mail your desire to

labinfo@horiba.com

Sizing techniques

Particle Analysis – choices

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

particle size distribution
• Quick, repeatable
• Most common technique
• Suspensions & powders

Laser diffraction
Suspension Powders
Silica
~ 30 nm
Coffee Results
0.3 – 1 mm
14 100
90
12
80
10 70
60
8
q(%)
50
6
40
4 30
20
2
10
0 0
10.00 100.0 1000 3000
Diameter(µm)

What is image analysis?
Take a picture, analyze

for size and shape

Why image analysis?
 Replace sieves (really!)

 Verify/supplement laser diffraction results (orthogonal technique).
 Access larger sizes than laser diffraction
 Need shape information, for example due to importance of powder flow
 Particle size is a critical quality attribute (CQA) in the realm of Oral solid
dosage (OSD) manufacture.
 Particle size directly relates to:
 Flowability
• Blend uniformity
• Compressibility
• Dissolution rate
• Bioavailability Same size (cross section),
but behave very differently.

Why image analysis?
Replace Sieves
 Tend to wear over time. It is difficult to tell when

sieve results are “drifting” due to wear
 Results depend on nature of shaking and loading

leading to operator-to-operator variations in results
 Small number of size classes

Courtesy Wikipedia user © BMK (de.wikipedia.org)“
//commons.wikimedia.org/wiki/File:Laboratory_sieves_BMK.jpg

Effect of shape on flow
• Yes, I assumed density doesn’t matter.
• Roundness is a measure based on particle perimeter.
qc

Multiparticulate drugs
Shape affects drug release profile

Common Questions
How many particles?
Minimum Particle Size
Maximum Particle Size
Accuracy
<USP> 776: Mean
 s   sz 
2
u  z  n 
 n u
u=uncertainty
z=confidence coefficient (often ~2, see a statistics book)
s=standard deviation of distribution (width)
n=number of particles measured
Example: for uncertainty of + 5 µm with st dev= 20 µm

Must measure 61 particles
 sz   201.96 
2 2
n     62
u  5 
Implies normal particle size distribution, greater than 30 particles, and known
standard deviation.

<USP> 776: Standard Deviation
 n  2 n 
s  2     s  2 
2
 a   b 
=Moment of chi squared distribution (see a statistics book)
s=estimated standard deviation of distribution (width)
n=number of particles measured
These limits are asymmetric around the standard deviation.
Assumes normal particle size distribution, greater than 30 particles, and known
standard deviation.

50 particles
1.0
Volume Based Distributions
Differential Distribution Cumulative Distribution

0.8
All Particles
Measurement 1
0.6
Measurement 2
0.4
0.2
0.0
0.05
0.04 Measurement 1
0.03 50 particles
0.02
0.01
0.05
0.04 Measurement 2
0.03 50 particles
0.02
0.01
0.00
5 6 7 8 9 2 3
100
Circular Diameter, m
400 particles
1.0
Differential Distribution Cumulaltive Distribution

Volume Based Distributions
0.8
All Particles
0.6 Measurement 1
Measurement 2
0.4
0.2
0.0
0.04
Measurement 1
0.03
400 particles
0.02
0.01
0.05
0.04
Measurement 2
0.03
400 particles
0.02
0.01
0.00
5 6 7 8 9 2 3
100
Circular Diameter, m
Compare With USP

How Many Particles?
 Some materials have a distribution such that

SD/Mean ~ 1.
 To obtain reliable mean values, measure

~1500 particles.
 To obtain more details about the distribution,

(10x?) more particles need to be measured.

Over to Darren…

Minimum Size: Pixels
Detection of particles
One pixel is element of a projection when at least half of the pixel is covered.
21
Maximum size
Large particles cannot

have been measured
properly even they fit
in the frame.
22
Maximum size
The probability of large

particles touching the
edge of the frame is higher
than for smaller particles.
 Large particles cannot

have been measured
sufficiently.
 Upper limit of
measurement range
23
Accuracy
• Is that the “real size”?
• Image analysis uses actual pictures to extract size.
• Calibration with a reticle.
Air force target PSA300 calibration target

24
How Image Analysis is done
• IA is the techniques of processing images through algorithms that

manipulate the numerical representation of the images to obtain useful
information.
• Output information may be an image or information associated with that

image, such as data on features, characteristics, bounding boxes, or mask
• With the ability to measure particles in a number of ways comes the decision
of what way to report those measurements.
©2020, Innopharma Technology Ltd. 25

Main Steps in Image Analysis
•Image
Visualization Acquisition
Image •Thresholding
digitization
Image •Segmentation
Processing
Feature of •Measurement
Interest
•Statistical
Data Analysis
©2020 Innopharma Technology Ltd. 26

Image Capture
Image Acquisition
Image Processing
Image digitization

Image Capture
ISO 13322-2
ISO 13322-1
Static and Dynamic IA: one is where the particles measured are stationary, the other measures particles in motion
©2020, Innopharma Technology Ltd. 28

Acquiring images
We want a good microscope and nice sharp images.

Pay attention to lighting and focus.
No Yes
29
Dispersing a sample (for acquisition)
Often want to spread particles out so that they don’t touch.
No Yes
30
Analog to Digital
0 0 0 0 0 0 0 0 0 0
0 0 0 80 100 97 180 190 0 0
0 0 222 90 150 110 240 255 180 0
0 80 245 80 100 120 205 210 230 0
0 15 210 111 96 63 201 222 240 0
0 180 190 135 97 91 110 2 230 0
0 240 255 205 180 190 55 255 219 0
0 205 210 175 240 255 110 150 55 0
0 0 45 185 205 210 88 255 0 0
0 0 0 0 0 0 0 0 0 0
Analog Image Digital Image Pixel Quantization
31
Segmentation
This can be done with software rules (such as look at
curvature), but generally, it is better to have a good dispersion.
There are clever illumination schemes to help with this…

32
.
Overlapping (Segmentation)
0 0 0 0 0 0 0 0 0 0
0 0 0 80 100 97 180 190 0 0
0 0 222 90 150 110 240 255 180 0
0 80 245 80 100 120 205 210 230 0
0 15 210 111 96 63 201 222 240 0
0 180 190 135 97 91 110 2 230 0
Two 0 240 255 205 180 190 55 255 219 0
0 205 210 175 240 255 110 150 55 0
Overlapping 0 0 45 185 205 210 88 255 0 0
Particle 0 0 0 0 0 0 0 0 0 0
Analog Image Digital Image Pixel Contour Amplitudes
33
Measurement: Particle Size
xarea
xc min
“diameter over “length”
“width” projection surface”
Major, minor
xFe max diameters
xc min A
Width is best suited

Shape parameters can
for comparison with
be calculated!
sieves !
xarea

Measurement: Particle Shape
Aspect ratio Eccentricity
= Feret Min
Feret Max
= Feret Max
Feret Min
= Feret Max Eccentricity is measured between 0 – 1

Feret Perp. to Feret Max 0 being completely spherical, major
diameter = minor diameter
Three different numbers

Measurement: More particle shapes

The PSA300
• Turnkey System
More time getting results and
less time engineering
• Automated
Faster
Less operator labor
Less operator bias
• Powerful Software Features
Image Enhancement
Particle separation
• Separate Disperser Option
More flexible sample preparation
37
The Eyecon2
• Real-Time particle Size Distribution and shape

• Use in:
• Research & development
(QbD/DoE/CPP/CQA)
• Scale up
• Tech transfer
Use on:
• Fluidised Bed Coating,
Granulation, Drying
• Twin Screw Granulation
• Roller Compaction/Milling
• Extrusion, Spheronisation
38
Conclusions
• Image Analysis is good for

Replacing Sieves
Size
Shape
Supplementing other techniques
• Watch out for

Sample preparation
Image quality
Measure enough particles
39
Where is PSA and image analysis going?

Machine Learning – Supervised Example
Image Label Example: Supervised
Image Classification
Dog
Predict
Cat
Bird Cat
(90% sure)
Cow
Learn
Elephant Bird
(70% sure)
Rat
Tortoise Elephant
(20% sure)

Machine Learning – Supervised vs Unsupervised
Supervised Machine
Learning Learns
Training Data
Labelled Test Predictions Outputs stats e.g.

Data accuracy of prediction
Test
Data
Unsupervised Machine
Learning Learn e.g.
find a pattern
Make Predictions
Raw
unlabeled
Data
Neural Networks
Hidden
Layers
Input Weight
Output
2
Weight Weight
1 3
Raw Images
PSD
Labeled Data

Machine Learning
Easy Right?

Questions?
• www.horiba.com/us/particle
• Jeffrey Bodycomb, Ph.D.

• Product Line Manager
• HORIBA Scientific
• jeff.bodycomb@horiba.com
• 800-446-7422
• Darren McHugh
• Product Manager
• Innopharma Technology Ltd
• mchughd@innopharmalabs.com
45
46

Modern Particle Characterization Techniques Image Analysis

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Modern Particle Characterization Techniques Image Analysis

Uploaded by

Copyright:

Available Formats

Modern Particle Characterization

©2020, Innopharma Technology Ltd 1

© 2020 HORIBA, Ltd. All rights reserved. 2

Did you sign up for our newsletter?

Receive regular updates and news on the

Send us a chat or e-mail your desire to

© 2020 HORIBA, Ltd. All rights reserved. 3

© 2020 HORIBA, Ltd. All rights reserved. 4

© 2020 HORIBA, Ltd. All rights reserved. 5

• Converts scattered light to

• Most common technique

• Suspensions & powders

© 2020 HORIBA, Ltd. All rights reserved. 6

© 2020 HORIBA, Ltd. All rights reserved. 7

Take a picture, analyze

© 2020 HORIBA, Ltd. All rights reserved. 8

 Replace sieves (really!)

© 2020 HORIBA, Ltd. All rights reserved. 9

 Tend to wear over time. It is difficult to tell when

 Results depend on nature of shaking and loading

 Small number of size classes

© 2020 HORIBA, Ltd. All rights reserved. 10

© 2020 HORIBA, Ltd. All rights reserved. 11

© 2020 HORIBA, Ltd. All rights reserved. 12

How many particles?

Minimum Particle Size

Maximum Particle Size

Example: for uncertainty of + 5 µm with st dev= 20 µm

© 2020 HORIBA, Ltd. All rights reserved. 14

These limits are asymmetric around the standard deviation.

© 2020 HORIBA, Ltd. All rights reserved. 15

Differential Distribution Cumulative Distribution

Differential Distribution Cumulaltive Distribution

© 2020 HORIBA, Ltd. All rights reserved. 18

 Some materials have a distribution such that

 To obtain reliable mean values, measure

 To obtain more details about the distribution,

© 2020 HORIBA, Ltd. All rights reserved. 19

© 2020 HORIBA, Ltd. All rights reserved. 20

Large particles cannot

The probability of large

 Large particles cannot

• Is that the “real size”?

• Image analysis uses actual pictures to extract size.

• Calibration with a reticle.

Air force target PSA300 calibration target

• IA is the techniques of processing images through algorithms that

• Output information may be an image or information associated with that

©2020, Innopharma Technology Ltd. 25

©2020 Innopharma Technology Ltd. 26

©2020 Innopharma Technology Ltd. 27

©2020, Innopharma Technology Ltd. 28

We want a good microscope and nice sharp images.

0 0 0 80 100 97 180 190 0 0

0 0 222 90 150 110 240 255 180 0

0 80 245 80 100 120 205 210 230 0

0 15 210 111 96 63 201 222 240 0

0 180 190 135 97 91 110 2 230 0

0 240 255 205 180 190 55 255 219 0

0 205 210 175 240 255 110 150 55 0

0 0 45 185 205 210 88 255 0 0

Analog Image Digital Image Pixel Quantization

There are clever illumination schemes to help with this…