Slide 1: FLOW PROPERTIES OF POWDERS
SEGREGATION
SOLID STATE STABILITY
Slide 2: CONTENTS
1.FLOW PROPERTIES OF POWDERS
INTRODUCTION
FACTORS INFLUENCING FLOW PROPERTIES
IMPROVEMENT OF POWDER FLOW
MEASUREMENT OF FLOW PROPERTIES
2.SEGREGATION
INTRODUCTION
PARTICLE PROPERTIES THAT AFFECT SEGREGATION
APPROACHES TO RECTIFY SEGREGATION
3.SOLID STATE STABILITY
ELEVATED TEMPERATURE STUDIES
STABILITY STUDIES UNDER HIGH HUMIDITY CONDITIONS
PHOTOLYTIC STABILITY
STABILITY TO OXIDATION
Slide 3: The flow properties of powder plays an important role in dosage form manufacturing process.
Importance of Flow-property studies of powder material
1.Weight uniformity
2.Content uniformity
3.Hardness
4.Disintegration
5.Speed of production
6.Scientific design of formulations and processing equipment
FACTORS INFLUENCING THE FLOW OF POWDERS
1.Particle size
2.Size distribution
3.Particle shape
4.Moisture and static charge
5.Electrostatic effects
6.Powder cohesion and storage compaction
7.Effect of temperature
Slide 4: PARTICLE SIZE
If size (or) dimensions of particles altered
Particles change in nature
flow of particles changed
Slide 5: In general larger particle flow faster than smaller particles? Particles less than 100µm in diameter
cohesive
Poor flow Particles above 1000µm in diameter
Free
Good flow
Slide 6: SIZE DISTRIBUTION
Size distribution is carried out by using proper amounts of fines.
PARTICLE SHAPE AND SURFACE MORPHOLOGY
The irregular shapes of particles flow become slowly.
Scaning electron microscope.
The mixtures containing irregularly shaped particles segregated slowly.
The flowability of powders increase with increasing sphercity, indicted by shape index ῳ and measured by image analyser.
Slide 7: MOISTURE AND STATIC CHARGE
The effect of moisture on flowability of particles varies from powder to powder.
The particles become cohesive due to moisture absorption.
Absorbed moisture in solids can exist in two forms1.unbound state2.As a part of crystal structure
The effect of moisture on flow of powder measured by determination of tensile strength.
Slide 8: ELECTROSTATIC EFFECTS
The charged material show poorer flow than uncharged material.
Particles acquire static charge
Grinding
Attrition
collision
mixing
sieving
Moisture
Particle-wall collisions, particle-particle collisions, or particle fragmentatoin
Electro static charge may be possitive or negative.
+ve particles plastic surfaces
-ve particles metal or glass surfaces
Slide 9: POWDER COHESION AND STORAGE COMPACTION
A solid remains at rest or storage in a hopper or bin , it can become more cohesive and difficult to flow.
Flow chacteristics depends on
Intrinsic cohesiveness of the material
Temperature of storage
Hopper and bin load levels
Time of storage
Vibratory forces
Slide 10: METHODS OF IMPROVING THE FLOW PROPERTIES OF POWDERS
1.INCREASING THE AVERAGE PARTICLE SIZE
Large particles are less cohesive and fast flow
Granules are commonly used in tablet manfacture
2. PRODUCING THE POWDER IN THE FORM OF SPHERICAL PARTICLE
Spherical partcile flows easily
Produced by spray drying
3. USE OF GLIDANT
Improve the flow properties of powder and granules
Ex:- colloidal silicone, talc, and starch
Slide 11: MECHANISM OF GLIDANT ACTION
Dispersion of static charge
Adsorption of gases and vapours in the system
Physical seperation of particles
Adsorption of Glidant particles to granulation surfaces
Coat the host particles completely
EFFECT OF GLIDANT
Particle size and shape
Degree of mixing
Concentration of glidant
Moisture content
Slide 12: MEASUREMENT OF FLOW PROPERTIES
1. Angle of repose
2. Compressibility index
3. Shear cell method
4. Hopper flow rate
Slide 13: 1. ANGLE OF REPOSE:-
Angle of repose is defined as the angle of the free surface of a pile or heap of powder to the horizontal plane.
Characterize the flow properties of solids. If material is not cohesive
Flows well
Low heap If material is cohesive
Poor flow
High heap
Slide 14: The standard method include pouring the powder onto the plat surface and measuring the angle of the resulting heap
tan = h/r
Slide 15: Tan = h/r
h = height of the heap
r = radius of the heap
Protractor is commonly used to measure the base and height of the heap.
Slide 16: 2. COMPRESSIBILITY INDEX:-
It demonstrates the relation between the flow and compressibility of
Powder.
%Compressibility = (tapped density – poured density /tapped density ) 100
Slide 17: HAUSNER RATIO
Hausner predict the flow properties of powder by using interparticle friction
Hausner ratio = tapped density /poured density
Slide 18: 3. SHEAR CELL DETERMINATIONS :-
Characterize the flowability from the behavior of powder in a shear cell
Sand witch of powder
The powder bed was subjected to shear and its applied load for shear also noted
Graph plotted between shear stress and applied load
Flow factor can be obtained by determining the reciprocal slope of a curve.
Slide 19: 4. HOPPER FLOW RATE
Simplest method
Simple shutter is placed over the hopper outlet and powder is filled
The shutter is then removed and time taken for complete discharge of powder is taken
The ratio of powder mass to time taken for complete discharge gives flow rate
FLOW RATE = POWDER MASS / TIME PERIOD
Slide 20: SEGREGATION
segregation × mixing
segregation
Difference in mobility of mixture components
Differences in partical size,shape,density and surface characteristics
FACTORS FOR SEGREGATION IN POWDER BED
un uniform particles
Vibration
Mixing and handling
Free flowing particles or cohesion less
Slide 21: PARTICLE PROPERTIES THAT EFFECT SEGREGATION
1.particle size
2.particle density
3. particle shape
1.PARTICLE SIZE
Difference in particle size is the main cause of segregation
smaller particles
void spaces of larger particles
percolation segregation
Slide 22: Kinetic energy of larger particles > kinetic energy of smaller particles
Larger particles move greater distance than smaller particles
Trajectory segregation
Slide 23: During mixing very small particles are blown upward by turbulent air
The small particles or dust will sediment and subsequently form a layer on top of the coarse particles
Elutriation segregation or dusting out
Slide 24: 2.PARTICLE DENSITY
More denser particles segregate faster than less denser than particles
Difference in particle density results in trajectory segregation
3.PARTICLE SHAPE
Intensity of segregation is more in spherical particles than non spherical particles
Slide 25: APPROACHES TO RECTIFY SEGREGATION
Selection of particular size fraction
Milling of components
Controlled crystallization
Selection of similar densities of excipients and active components
Production of ordered mix
Granulation of powder mixture
Prevent the movement and vibration of powder bed
Slide 26: SOLID STATE STABILITY
Various stability studies conducted are
1.Elevated temperature studies
2.Under humidity condition studies
3.Photolytic stability
4.Stability to oxidation
Slide 27: ELEVATED TEMPERATURE STUDIES
The elevated temperatures most commonly used are 50ºc ,60ºc,70ºc, and 85ºc,121ºc
Conduct the same experiments at room temperature(30ºc,70%RH)
Samples may be done at
3 month intervals during the first year
6 month intervals during the second, and yearly thereafter
The samples stored at high temperatures are examined for physical and chemical changes at frequent intervals and any change, when compared to appropriate control (usually sample stored at 5 ºc or 20 ºc
To confirm the results obtained from accelerated stability studies and room temperature
The drug content is estimated by using a stability indicating assay method
Slide 28: STABILITY UNDER HUMIDITY CONDITIONS
In the presence of moisture many drugs hydrolyze or oxidize by react with other ingredients.
Expose the solid drug to different relative humidity conditions
Controlled humidity environment can be produced by using laboratory desicator containing saturation solutions of various salts
Slide 29: PHOTOLYTIC STABILITY
Many drug substances are fade or darken on exposure to light
Extent of degradation is small and limited to exposed surface itself
Protected by
1.Stored in amber colour glass or opaque container
2.By incorporating photostable dye
exposure of the drug substance to 400 and 900 foot candles (fc) of illumination for 2to 4 weeks
Over these period samples are withdrawn and examine for any loos of colour and
Chemical stability and compared with that of samples stored under same conditions but protected from light
Change in appearance is quantified by using spectroscopic methods
Slide 30: STABILITY TO OXIDATION
Stability to oxidation was carried out by using the hydrogen peroxide in the concentration range of 3to 30%
some drugs extensive degradation is seen when exposed to even 3% of hydrogen peroxide for very shorter time period at room temperature
Some drugs exposure to high concentration of hydrogen peroxide even under extreme condition does not cause any significant degradation
Usually 40% oxygen atmosphere allows for a rapid evaluations
Results should be compared against those obtained under ambient atmosphere
Slide 31: BIBLIOGRAPHY
J.T. Carstensen, Principles and practices of drug stability, “solid state stability” by markel dekker.inc,2nd edition.1995. page.no-249-250
2. Stephen. A.howard, Flow properties of solids, “ Encyclopedia of pharmaceutical technology” by markel dekker,2nd edition, volume-2, page no-1264 -1283
3. S.J. Carter, The flow properties of powders and granules, “Tutorial pharmacy” by CBS Publishers and distributors, 6th edition, 2000, pg no-223 -229
4. N.K. Jain, Flow ,cohesiveness and compressibility, “Professional pharmacy” by vaallabh prakashan, 5th edition,1998 pg no-145-147
5. Harry G. Brittain, Physico chemical properties, ,”Physical characterization of pharmaceutical solids” by markel dekker.inc,1995 pg.no-281-301
6.C.V.S Subramanyam, Drug stability, “physical pharmaceutics “by vallabh prakashan,5th edition,2000,page.no-51-84
Slide 32: Thank you