powder flow: the missing link in the evolution of … · powder flow: the missing link in the...
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Arjen P. TinkeJanssen R&DDepartment of Chemical Technology and Process Control (CTPC)Turnhoutseweg 30B‐2340 Beerse (BELGIUM)
Powder Flow: the missing link in the evolution of powder characterization
Colloids
Suspensions = Solids + Liquids
Powders = Solids + Liquids + Gasses
A ‘suspension’ is not so much different than a ‘powder’
Is it?...Particle‐particle interaction
• Cohesion• Repulsion• Friction• Interlocking
Product variables that influence behaviour• Size• Shape• Surface texture (roughness)• Surface area
External variables that influence behaviour• Consolidation• Aeration• Flow (shear) Rate• Moisture• Electrostatic Charge• Storage Time• Porosity• Potential for electrostatic charge
• Hygroscopicity• Hardness / Friability• Amorphous content• Density• Cohesion• Adhesion• Elasticity• Plasticity
Powder
Particle Size May Say It AllParticle size may have a large effect on bulk behaviour
• Flowability / Rheology• Sedimentation rate• Abrasiveness• Explosion• Dissolution• etc.
Dissolution rate constant
Noyes‐Whitney equation
Particle size dependency
Laser DiffractionApplication area• QC• R&D
Added value• Golden standard• Black box
Sub Micron Sizing
Particle Size Distribution Imaging Bulk Characteristics
Solid State Foreign Material IdentificationCharacteristics
• Laser Diffraction• Dynamic Light Scattering• (Automated) Static Image Analysis• Dynamic Image Analysis
• SEM• Optical Microscopy
• DSC• XRD• Dynamic Vapor Sorption
• Optical Particle Counting• Dynamic Image Analysis
• IR and Raman Microscopy
• Helium Pycnometry• Gas Adsorption
Particle Characterization
Bench Top SEM
d10 (m) d50 (m) d90 (m)
Batch A 1.8 5.7 11.4
Batch B 1.9 5.9 12.3
We’re Missing SomethingA
B
Fluid Imaging
Drug Substance
Chemical Purity
Physical Purity
Powder Characteristics
Quality Aspects
Powders in Pharm Industry
Cohesive
Aeratable
Sand‐like
Spoutable
Milling chamber completely filled with powder
Flow Obstruction
Obstruction of exit holes
Flowability Brittleness Milling
Shear Impact Intended BreakageNon‐Intended Breakage
Crystallization
ConditioningPackaging & Transport
• Cohesion• Friction• Interlocking
• Mechanical Properties
• Particle Size Distribution• Up‐ and Down‐Scaling• Modelling• PAT
• Structural Disorder• Relaxation• Surface Energy
• Tribo Electrification(Static Charge)
• Particle Size• Morphology• Product Characteristics (e.g., flowability, mechanical properties)
Solid‐Liquid Separation (incl. Drying) PATMorphology
Powder Technology
Dynamic Image Analysis
Powder Flowability Powder Rheology Particle Shape Distribution
Surface Energy Surface Charge Mechanical Properties/ Structure
• Bulk‐and‐Tap Density• Static Angle‐of‐Repose • Dynamic AOR
• Inverse GC• TAM
• Faraday cup• Charge decay analysis
• Nano identation• Micro hardness testing
• Powder Rheology
Powder Characterization
• (Automated) Static Image Analysis –Optical Microscopy
Particle ShapeStatic Image Analysis
For rectangular particlesthe laser diffraction (LD)particle size distributionprofile can be calculatedfairly well from the length and the width of the particles.
Powder FlowabilityU.S. Pharmacopoeia<267> Hg porosimetry<429> Laser diffraction<601> Inhalation<616> Bulk and tapped density<699> Helium pycnometry<776> Optical microscopy<786> Sieve testing<811> Powder fineness<846> Specific surface area<1174> Powder flow
Funnel Static AOR BTD Dynamic AOR
Powder Rheology
Batch (*)(g.cm‐3)
[o](g.cm‐3)
[n](g.cm‐3)
n½ H[n] C[n]
Batch C 1.30 0.40 0.45 16.0 1.12 10.3 14.1
Flow Behaviour C HExcellent 10 1.00‐1.11Good 11‐15 1.12‐1.18Fair 16‐20 1.19‐1.25Passable 21‐25 1.26‐1.34Poor 26‐31 1.35‐1.45Very poor 32‐37 1.46‐1.59Very, very poor > 38 > 1.60
Bulk-and-tap density data(*) - measured with helium pycnometry[o] - bulk density (g.cm-3)[n] - tap density (g.cm-3)n½ - compaction kinetic factorH[n] - Hausner ratio (H[n]=[n]/ [o])C[n] - Compressibility factor, or Carr index (H[n]=100/(100-C[n]) - characteristic relaxation time obtained from the fit of the experimental results
Batch Cohesion(kPa)
UYS(kPA)
MPS(kPA)
FF AIF(o)
Measurement Vessel
Batch C 2.82 11.2 20.7 1.85 36.4 25 mm 10 mL
Shear cell test resultsUYS - Unconfined Yield StrengthMPS - Major Principle StressFF - Flow FunctionAIF - Angle of Internal Friction
Type of Flow FFFree‐flowing 10 < FF Easy‐flowing 4 < FF < 10Cohesive 2 < FF > 4
Very cohesive and non‐flowing
FF < 2
Classification of powder flowability after Jenike
Scale of flowabilityData taken from USP <1174>
FT4 Powder TesterDynamic Flow• BFE ‐ Basic Flowability Energy (mJ)• SE ‐ Specific Energy (mJ/g)• SI ‐ Stability Index• FRI ‐ Flow Rate Index• AE ‐ Aerated Energy (mJ)• AR ‐ Aeration Ratio• CE ‐ Consolidated Energy
Bulk• CBD ‐ Conditioned Bulk Density (g/mL)• CPS ‐ Compressibility Percentage (%)• PD ‐ Pressure Drop across the Powder Bed
Shear• C ‐ Cohesion (kPa)• FF ‐ Flow Function• AIF ‐ Angle of Internal Friction (o)• WF ‐ Wall friction
Process• Flow (Obstruction)• Conveying• Segregation• Attrition• Caking• Electrostatics• Moisture• Agglomeration• etc.
‘Powder Flow’
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Supportive Data
Conclusions• PSD measurements work well in QC, but are not sufficient in R&D
• ‘Powder Flow’ is a broad area, which is more about ‘Flow Obstruction’ than about ‘Flow’
• PHARMACOPOEIA• Relevant for QC• Less for R&D
• HOWCharacterization of ‘Powder Behaviour’
• Flowability testing• Powder rheology• Powder testing (FT4)
• WHYCharacterization of ‘Powder Characteristics’
• Image analysis• Static charge• Surface energy• Etc.
Thank you for your attention!
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