Powder Flow Fundamentals,
Characterization, and
Pharmaceutical Applications
Changquan Calvin Sun © 2015
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Outline
1. Introduction
2. Methods for characterizing powder flowability
3. Strategies for improving powder flowability
(crystal and particle engineering)
4. Conclusions
2
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Pharmaceutical Relevance of
Powder Flow
• Powder transportation and storage
(silo, drum, bin)
• Flow through a hopper
• Emptying out from a blender
• Filling a die cavity
• Filling a capsule shell
1.
2.
3.
4.
3
Poor quality products (CU, elegancy)
Lower production rate
Rejected batches
Product recalls
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Powder – a Fourth State of Matter?
liquid
powder
solid
Mechanical strength – characteristic of a solid
Flowing – characteristic of a liquid
Concentrated dispersion of solid particles in air
Flow of powder is history dependent!
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Nature of Powder Flow
Flow = movement of particles
Initiation of powder flow is due to force imbalance
– gravity
– adhesion (molecular interactions)
– mechanical interlocking (friction)
– electrostatic force
5
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Gravity vs. Adhesion
6
1.
Larger size → better flow
2.
Larger particle-particle separation → better flow
K. Kendall, 1994, Science, 263:1720 - 1725
Unconfined Yield Strength, fc
Stronger powder bed → more difficult to initiate flow
(or fc A)
D. Schulze, Flow Properties of Powders and Bulk Solids, http://www.dietmar-schulze.de/grdle1.pdf
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Common Flow Behavior – 1. erratic flow
http://www.jenike.com/Solutions/poorflow.html
rathole
8
arch
•
A result of alternating occurrences between an arch and a rathole
•
Always problematic
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2. Funnel Flow & 3. Mass Flow
http://www.jenike.com/Solutions/poorflow.html
1. First-in, last-out flow sequence
1. First-in, first-out flow sequence
2. Worsened segregation
2. Reduced segregation
3. Tends to be problematic
3. Process friendly
Same powder, different flow behaviors!
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A Key Point
Powder flow also depends on equipment design and processing conditions!!
Moisture
Processing
conditions
Particle shape
Particle size
Powder flow
properties
Chemical nature
Surface roughness
Equipment
design
This is one reason why scale up can be challenging.
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Flow
behavior
Effects of Hopper Design on Powder Flow
Funnel flow
Mass flow
Same powder, different flow behavior!
11
Methods for characterizing
powder flowability
•
•
•
•
•
•
12
Compressibility index
Flow through an orifice
Angle of repose
Shear cell
Avalanche tester
Powder rheometry
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Compressibility index / Hausner ratio
(1) the bulk volume (VO) or bulk density (rbulk)
(2) the final tapped volume (Vf) or tapped density (rtapped)
Compressibility
Index (%)
10
or
Flow Character
Hausner Ratio
Excellent
1.00–1.11
11–15
Good
1.12–1.18
16–20
Fair
1.19–1.25
21–25
Passable
1.26–1.34
26–31
Poor
1.35–1.45
32–37
Very poor
1.46–1.59
>38
Very, very poor
>1.60
Carr, R.L. Evaluating Flow Properties of Solids. Chem. Eng. 1965, 72, 163–168
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Flow Through an Orifice
1. Materials must flow, not useful for
cohesive powders (plugging)
cylinder
2. Flow rate (g/s, or mL/s) is
independent of h, if h > d1
3. d1 > 6 diameter of particles
powder
4. The diameter of cylinder > 2*d1
5. Rate of powder flowing through is
orifice (d1)
recorded by a balance.
h
balance
Minimum orifice diameter for flow is a
common variation of this technique.
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(recommended set up)
Angle of Repose
• related to interparticulate friction or resistance to movement
between particles
• segregation of material and consolidation or aeration of the
powder as the cone is formed
Flow Property
a (degrees)
Excellent
25–30
Good
31–35
Fair—aid not needed
36–40
Passable—may hang up
41–45
Poor—must agitate, vibrate
46–55
Very poor
56–65
Very, very poor
>66
Carr, R.L. Evaluating Flow Properties of Solids. Chem. Eng. 1965, 72, 163–168
15
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a
Stationary funnel and base
Variations to Angle of Repose
Flow through an orifice
Classic angle of repose
(retrieving funnel)
Avalanche
(dynamic angle of
repose)
D. Schulze, Flow Properties of Powders and Bulk Solids, http://www.dietmarschulze.de/grdle1.pdf
Issues with these techniques
• Sensitive to operators
• Sensitive to apparatus used (size,
vibration, etc.)
• Only consider particle-particle
interactions
• Empirical in nature
• Not intrinsic powder properties
• Single point measurements
• Relevant to flow under zero stress
Are powders stress-free during manufacturing?
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Shear cell
Benefits of Shear cell
•
•
•
•
•
D. Schulze, Flow Properties of Powders and Bulk Solids,
http://www.dietmar-schulze.de/grdle1.pdf
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Scale-independent
Clear physical meaning
An established classification scheme
An established reference powder for high
speed tableting
Widely accepted in engineering and
materials science research
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Setting the Bar for Powder Flow
70 rpm
90 rpm
3.00
Avicel PH102
7/32
Wt. RSD (%)
2.50
11/32
16/32
2.00
oval
1.50
1.00
0.50
0.00
0
2
4
6
8
10
12
14
16
time (min)
Excellent die filling
performance
Not processible
Avicel PH102 lies near the boundary between acceptable and non-acceptable
regions of powder flow properties for high speed tableting.
Sun, 2010, Powder Technol., 201:106-108
18
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Ways to Improve Powder Flow
1.
2.
3.
4.
5.
6.
7.
19
Size enlargement (granulation)
Surface smoothing
Reducing cohesion
Optimizing moisture content
Particle rounding (shape)
Increasing particle density
Increasing gravitational force
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Effect of Particle Size
Better flowability
Hou & Sun, J Pharm Sci, 2008, 97:4030-4038
20
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Effect of Particle Shape
4
Avicel PH200
Celphere SCP-100
f c (kPa)
3
D50 = 229 mm
Celphere CP-102
2
D50 = 128 mm
1
D50 = 165 mm
0
0
5
10
15
20
25
30
35
Major principal stress (kPa)
Smaller but more spherical MCC particles flow better than larger elongated particles!
Hou & Sun, J Pharm Sci, 2008, 97:4030-4038
21
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Effect of Surface Texture
unconfined yield strength (kPa)
2.0
10 kPa
0% H2O
1.5
Better flowability
1.0
5% H2O
0.5
-5
0
5
10
15
20
25
30
35
Water Level (%)
MCC (Avicel PH101) granulated with various
amounts of water (HSWG) and dried
15% H2O
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Shi et al., 2011, Powder Technol, 208:663 - 668
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Effect of Crystal Chemistry
unconfined yield strength (kPa)
monohydrate
9.0
8.0
Weight gained (%)
Conditioned over night at 60% RH.
12
10.0
7.0
6.0
Citric acid
69.9% RH at 20 oC
5.0
4.0
3.0
Citric acid
2.0
wt. gained if fully hydrated
1.0
anhydrate
0.0
0
CA anhy.
10
CA monohy.
8
cohesive
6
4
easy flowing
2
free flowing
0
30
60
90
120
0
23
Sun, J Pharm Sci, 2009, 98:1744-1749
10
15
20
Major principal stress (kPa)
Time (days)
a anhydrate
5
b monohydrate
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25
30
Effect of Particle Density
12
Density corrected f c (kPa.cm3.g-1)
5
Avicel PH302
f c (kPa)
4
Avicel PH102
3
2
1
a
0
Avicel PH102
10
Avicel PH302
8
6
4
2
a
0
0
5
10
15
20
25
30
35
0
Major principal stress (kPa)
•
•
•
24
5
10
15
20
25
Major principal stress (kPa)
Particle-particle interactions are comparable based on fc
Higher density particles flow better
Density corrected fc accurately reflects flow behavior
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30
35
Reducing Cohesion
If gravity > adhesion, flow is not a major problem
•
•
Increased separation leads to reduced cohesion
Coated nano-particles act as
1) Spacers, to separate host particles
2) Ball bearing, to reduce friction
We used comilling for nanocoating.
25
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1.
Hybridizer
2.
Mechanofusion
3.
Theta composer
4.
Rotating fluidized bed coater
5.
Magnetically assisted
impaction coating
Surface Coating by Comilling
5000 X
Uncoated
Nanocoated
• Comilling - fast, readily available, scalable, & economical
• Avicel PH105 (Cohesive, a common tablet excipient)
• Fumed silica (Carb-o-sil, A common excipient)
Chatteraj et al, J Pharm Sci, 2011, 100:4943-4952
26
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Impact on Processibility
16
12
Nanocoated
Avicel PH105
Avicel PH105
The bar
Tensile strength (MPa)
Flow factor (ff)
10
8
6
4
12
Avicel PH102
8
4
2 MPa
2
0
0
Uncoated
PH105
Physical blend
Nanocoated
PH105
Uncoated
PH102
0
100
200
300
Compaction pressure (MPa)
Nanocoated Avicel PH105 (1% silica, 40 comilling cycles):
•
flow properties similar to Avicel PH102 (the bar)
•
Tabletability remains higher than Avicel PH102
Chatteraj et al, J Pharm Sci, 2011, 100:4943-4952
27
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400
Avicel PH102 - silica composites
1% silica
55
Flow factor
45
35
25
the bar
15
Better flowability
5
0.0
0.5
1.0
1.5
2.0
2.5
Silica loading (wt%)
Low intensity blending is as effective as comilling for Avicel PH102.
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Zhou et al, 2012, J Pharm Sci, 101:4259-4266
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Ibuprofen Formulation
25
Flow factor
20
15
10
5
75% ibuprofen
22% MCC (Avicel PH102)
3% Sodium Croscarmellose
0
no
silica
0.1%
silica
0.5%
silica
Representative of powders with flow problems observed on pilot plant equipments.
Zhou et al, 2013, Powder Technol. 249:290-296
29
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Comilling vs. Blending
25
Flow Factor
20
15
10
5
0
5 comilling
cycles
Blending 15'
Flow enhancement can be achieved through simple blending if the powder is not
very cohesive.
Zhou et al, 2013, Powder Technol. 249:290-296
30
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Conclusions
1. Understanding the interplay between cohesion and
gravity is central to solving powder flow problems
2. Flowability problems can be effectively addressed by
particle engineering
31
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Acknowledgements
AAPS
Abbott Laboratories
Boehringer Ingelheim
Cima Labs
FDA
Merck
NSF - CPPR
PhRMA Foundation
Univ. of Minnesota
Dr. Limin Shi
Dr. Qun Zhou
Dr. Sayantan Chattoraj
Dr. Qun Lu
Dr. Helen Hou
32
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