Micromeritics - Fundamental and Derived Properties of Powders

MICROMERITICS
Ms. Chitralekha G. Therkar
Assistant Professor
Dept. of Pharmaceutics
Siddhivinayak College of Pharmacy, Warora

Definition: It is the science and technology of small particles i.e.
powdered particles and it also deals with the fundamental and derived
properties of the powders.
 The unit of particle size is expressed in micrometer (μm), micron
(μ) and it is equal to 10-6 m.
 Generally, the size of larger particles can be expressed in terms of
millimetres (mm) and the size of smaller particles can be expressed
in terms of nanometres (nm).
Various units used to express the size of particles are,
 Millimeter - 10-3
 Micrometer - 10-6
 Nanometer - 10-9
 Angstrom - 10-10
 Picometer - 10-12
As particle size decreases, the surface area increases.
The knowledge and control of particle size is important in pharmacy
and material science.
Introduction

applications
1. To determine the Particle size
2. To determine the distribution of particles.
3. To determine the effective particle size for any novel preparation.
4. In clinical research.
5. In research, formulation and development.
The particle size and surface area of any particle can be related to
the physio - chemical and pharmacological properties of the drugs to
be incorporated in the formulation as follows,
 Release and Dissolution - Particle size and surface area
influence the release of a drug from a dosage form. Higher surface
area allows intimate contact of the drug with the dissolution fluids
and increases the drug solubility and dissolution.
 Absorption and Drug action - Particle size influence the drug
absorption and subsequently the therapeutic action. Higher the
dissolution, faster the absorption and hence quicker and greater
the drug action.

 Physical Stability - The particle size and the surface area in any
formulation influences the physical stability of the suspensions and
emulsions. Smaller the size of particle, better the physical stability
of the dosage form.
 Dose uniformity - Good flow properties of granules and powders
are important in the manufacturing of tablets and capsules.
Particle size range of different systems
SN Formulations Size range
1 Suspensions and Emulsions 0.5 μm to 10 μm
2 Flocculated suspension and coarse emulsion 10 μm to 50 μm
3 Fine particles 150 μm to 1 mm
4 Granules 1 mm to 3.5 mm

ParticleSize and Particle Size Distribution
In a collection of particles of more than one size, two properties are
important,
1. The shape and the surface area of the individual particle.
2. The particle size and distributions (Size range and number or
weight of particle)
The calculations are done visualizing an imaginary sphere and size of a
sphere is readily expressed in terms of its diameter as follows,
1. The surface diameter (ds) is the diameter of a sphere having the
same surface area as the particle.
2. The volume diameter (dv) is the diameter of a sphere having the
same volume as the particle.
3. The projected diameter (dp) is the diameter of a sphere having
the same area as the particle.
4. The stokes diameter (dst) is the diameter which describes an
equivalent sphere undergoing sedimentation at the same rate as the
asymmetric particle.

Particle Size Distribution
 Any collection of particles is usually polydisperse. Therefore it is very
necessary to know not only the size of a certain particles, but also how
many particles of the same size exist in the sample.
 Thus, we need an estimate of the size range present and the number
or weight fraction of each particle size.
 It represents the particle size distribution and from it we can calculate
an average particle size for the sample.
 When the number or weight of particles lying within a certain size
range is plotted against the size range, a frequency distribution curve
is obtained.
 It is important to estimate the particle size distribution because it is
possible for many formulations to have two samples with same
average diameter but different distributions.

Mean Particle Size
 Particle size is measured by mean, median and mode. Mean is the
average particle size.
 This means are of three different types namely, arithmetic, geometric
and harmonic. Arithmetic mean is the sum of particle size divided by
number of particles.
 The particles observed under microscope are classified into each size
range to know no. of particles in each size range as follows,
Size Range Mean No. of particles n x d
10 – 20 15 32 480
20 – 30 25 41 1025
30 – 40 35 63 2205
40 – 50 45 85 3825
50 – 60 55 52 2860
60 – 70 65 21 1365
70 – 80 75 06 450

Determination of particle size and particle size distribution is done by
following methods,
1. Optical Microscopy
 Light microscopy
 Scanning Electron Microscopy
 Transmission Electron Microscopy
2. Sieving
3. Sedimentation
 Andreasen Pipette Method
 Centrifugal Sedimentation Method
4. Particle volume measurement (Coulter Counter Method)
Methods

1. OpticalMicroscopy
For particle size in range of 0.2 to 100 micrometer the size is expressed
as projected diameter, which describes the diameter of a sphere
having the same area as that of asymmetric particle when observed
under microscope. For good size distribution atleast 300-500 particles
must be observed.
Methodology -
1. Prepare a powdered suspension whose size to be determined using a
vehicle in which it is insoluble. If it is slightly soluble then the
saturated solution of powder can be used.
2. A suspension drop is mounted on the slide and it is observed under
the microscope and the eyepiece of microscope is fitted with the
micrometer from which the particle size is estimated.
3. All particles observed in a field are counted through an eyepiece.
4. For ease in counting, the field can be projected on a screen or
photographed or can be counted with electronic scanners (Scanning
Electron Microscopy)

Advantages
 Easy and simple.
 It allows observer to view the particles particularly.
 Agglomeration and any contamination in powder can be detected.
 Particles in the dispersion must be free from motion which can be
achieved using coverslip.
Disadvantages
 Measured diameter represents only two dimensions i.e. length and
breadth, the depth is not obtained.
 Method is slow and tedious.
 Large sample is required.
AdvantagesandDisadvantages

2. SIEVING method
 For particles in the size range of 50 - 1500 μm are expressed as sieve
diameter which can be describes as the diameter of a sphere that
passes through the same sieve aperture as the asymmetric particle.
 Sieves for pharmaceutical testing are constructed from wired cloth
with square meshes, woven from wire of brass, bronze or stainless
steel and should not be coated or plated because there must be no
reaction between material of sieve and the substance to be sieved.
Methodology -
1. Sieves are arrange in a nest, stacked over one another with coarse at
the top and powdered sample is placed on the top of the sieve.
2. Sieve set is fixed to mechanical shaker and powder is shaken for a
certain period of time (20 mins) and the powder retained on each
sieve is weighed. And percent powder retained o each sieve is
calculated.
Note – This method gives the weight size distribution and the type of
motion influences sieving is vibratory motion followed by side tap
motion and rotary motion.

Advantages
1. Inexpensive
2. Simple method
3. Rapid with reproducible results.
Disadvantages
1. Lower limit is 50 μm, since it is limited by smallest size of sieve.
2. Moisture can leads to aggregation, leading to clogging and improper
results after procedure.
3. During shaking attrition leads to size reduction.
AdvantagesandDisadvantages

3.SEDIMENTATIONmethod
 This method is use for the particles of size range of 1 to 200 μm and
the particle size is expressed as stoke’s diameter which describes the
diameter of equivalent sphere having same rate of sedimentation as
that of asymmetric particle.
 It utilizes the apparatus known as Andreasen's pipette.
Methodology -
It consists of 550 ml stoppered cylindrical vessel with about 5.5 cm of
internal diameter with a vertical scale graduated from 0 to 20 cm on it.
There are 3 basic parts,
1. Stopper has an integral 10 ml bulb pipette fitted with a 2 way
stopcock and side tube for discharging sample.
2. Stem of pipette made of narrow bore tuning in order to minimize
the volume retained in the stem after each sampling.
3. Pipette is so fitted in the cylinder such that its lower tip is 20 cm
below the surface of the suspension.

Methodology
1. Transfer the sample up to the mark.
2. Vessel is stoppered and shaken to distribute particles uniformly.
3. Stopper is removed and two way pipette is placed and whole
assembly is kept undisturbed in constant temperature water bath.
4. At different time intervals the 10 ml samples are withdrawn using
2 way stopcock and collected in previously weighed china dish.
5. Sample are evaporated and weighed and are referred to as weight
undersize.
6. These weights are converted into cumulative weights.
7. Graph is drawn from data to get the curve of distribution.

4. Particle Volume Measurement
The coulter counter method is generally used to determine the particle
volume distribution.
Principle - When a particle suspended in a conducting liquid passes
through a small orifice on either side of which are electrodes a change in
electrical resistance occurs.
Instrumentation
 It consists of two electrodes one of which is dipped into a beaker
containing dilute suspension in an electrolyte (such as 0.9% NaCl).
 The other electrode is dipped into the electrolyte solution contained in
a glass tube which is immersed into the beaker containing the particle
suspension in the electrolyte.
 The glass tube has a very small orifice at its lower end through which
the particles are sucked into the inner glass tubes.

Micromeritics - Fundamental and Derived Properties of Powders

WORKING Methodology
 A known volume of suspension is pumped through an orifice so that
only one particle passes at a time through an orifice and a constant
voltage is applied across electrodes so as to produce a current.
 As the particle travels through orifice, it displaces its own volume of
electrolyte and this results in an increased resistance between the 2
electrodes and this is proportional to volume of the particle.
 This change in electrical resistance is termed as voltage pulse which
is related to particle volume. Voltage pulse is amplified and fed to a
pulse height analyzer.
 The pulse height is directly proportional to particle volume.
 The analyzer is previously calibrated in terms of a particle size for
different threshold settings.
 For a given threshold value pulses are electronically counted.
 By changing the threshold settings gradually number of particles of
each size range is obtained and thus particle size distribution can be
obtained.

Advantages
1. Operation is very rapid with a single count taking less than 30 sec.
2. Since large number of particles are counted results are more reliable.
3. Instrument can operate with particles between 0.5 and 1000
micrometer.
4. Since aperture is automatic the operator variability is avoided.
Disadvantages
1. Material has to be suspended in electrolyte liquid before the
measurement.
2. Aggregation of particles can give false results.
Advantages and Disadvantages

Specific Surface
The specific surface is the surface area per unit volume or per unit
weight. By taking the general case fort he asymmetric particles where
characteristic dimension is not defined, the surface area per unit volume
is given as,
Sv =
Surface area of particle
Volume of particle
Sv =
nsd2
nvd3
Sv =
s
vd
Where, n is the no. of particles.
d is the diameter of particle.
v is volume factor.
s is surface area factor.

SurfaceAreaDetermination
The surface area can be determined by two methods,
1. Adsorption Method
i. Adsorptionof solute on powder
ii. Adsorptionof gas on powder
2. Air PermeabilityMethod

Adsorption Method
Particles with the large specific surface are good adsorbents for the
adsorption of gases and solutes from solution. The amount of gas or
solute adsorbed on the sample of powder to form a monolayer is found
out from this data and the surface area of powder is determined.
1. Adsorption of solute on powder
 Solution of a suitable solute is first prepared in a medium in which
the adsorbent powder is insoluble.
Eg, Stearic acid in ethanol.
 Known amount of powder is then added to the solution and
contents are stirred for sufficient period of time.
 After equilibrium is attained the powder is filtered and amount of
solute remaining in solution is determined by suitable method.
 Difference between quantity added and the remaining quantity in
solution gives the quantity that adsorbed and then value obtained
amount adsorbed per gram of powder is calculated.

2. Adsorption of Gas on Powder
Instrument to be used for this process is called as Quantasorb.
Methodology -
 Powder whose surface area is to be determined is introduced into the cell
of instrument. The adsorbate gas i.e. nitrogen and helium which is an
inert gas and not adsorbed are passed through powder in cell.
 Thermal conductivity detector measures amount of nitrogen gas adsorbed
at every equilibrium pressure. Bell shaped curve is obtained on strip chart
recorder.
 Volume of nitrogen gas Vm adsorbed by 1 gm of powder when the
monolayer is formed is given by BET equation
=
Where,
V = volume of gas in cm3 adsorbed per gram of powder.
Vm = volume of nitrogen gas adsorbed in monolayer.
P0 = vapour pressure of liquified nitrogen at saturation.
b = constant
P = pressure.

AIR PERMEABILITY METHOD
Principle
 Resistance offered to the flow of a fluid such as air through a plug of
compacted powder is proportional to the surface area of a powder.
 i.e. greater the surface area per gram of the powder greater is the
resistance to flow.
 Surface area by air permeability is generally carried out with
instrument called Fisher Subsieve Sizer.
 Powder is packed in the sample holder as a compact plug.
 In this packing surface, contacts appear as a series of capillaries.
 The surface of capillaries is a function of surface area of powders.

Where,
A = cross sectional area of a bed
∆P= pressure difference of plug
T= time of flow in seconds
L= length of sample holder
ε= porosity of powder
Sw= surface area per gram of powder
η= viscosity of air
K= constant (5+0.5)
V= volume of air flowing through bed
 Kozeny carman equation is used to estimate the surface area,

Instrumentation
 Instrument is known as Fisher Subsieve Sizer.
 It is consist of the sample tube which contains packed powder sample
with 2 ends.
 One end is connected to air pump through constant pressure
regulator and other end is connected to manometer containing a
suitable liquid.

Working
 Air pump builds up air pressure and is connected to a constant
pressure regulator.
 Air is passed through a dryer to remove any moisture and then
allowed to flow through the packed powder.
 The flow of air is measured using manometer.
 Level of fluid in manometer indicates average diameter of the
particles which can be read from calculator charts supplied with
equipment.

Particle Shape
 The shape affects the flow and packing properties of a powder as
well as have some influence on the surface area.
 Surface area per unit weight is an important characteristic of a
powder when undertaking surface adsorption and dissolution rate
studies.
 A sphere has minimum surface area per unit volume.
 The more asymmetric a particle, greater is the surface area per unit
volume.
 A spherical particle is characterized completely by its diameter.
 As the particle becomes more asymmetric, it becomes increasingly
difficult to assign a meaningful diameter to the particle.
Surface area of spherical particle = πds
2
Volume of spherical particle = 1/6 πds
3
Where,
ds is surface diameter of spherical particle.

Fig. - Various shapes of particles.

Determination of particle shape
1. Microscopy Method
2. Light scattering method

1. Porosity -
Suppose a nonporous powder, is placed in a graduated cylinder:
the total volume occupiedis known as the bulk volume Vb.
bulk volume= true volume + volume of spaces between
particles.
The volume of the spaces, the void volume,V = Vb - Vp
Vp is the true volumeof particles.
The porosity or voids ε
of powder is determined as the ratio of void
volume to bulk volume.
Derived properties of powders

2- Densities of particles:
- Density is defined as weight per unit volume (W/V).
Types of densities:
A- true density
The true density, or absolute density,
of a sample excludes the volume of the
pores and voids within the sample.
B- bulk density (w/v) the bulk density value
includes the volume of all of the pores within
the sample.

Densities of particles
•During tapping, particles gradually
pack more efficiently, the powder
volume decreases and the
tapped density increases.

Derived properties of powders (Cont.):
3- Bulkiness = Specific bulk volume = reciprocal of bulk
density:
It is an important consideration in the packaging of powders.
The bulk density of calcium carbonate vary from 0.1 to 1.3, and
the lightest (bulkiest) type require a container about 13 times
larger than that needed for the heaviest variety.
(Bulkiness increases with a decrease in particle size).
In mixture of materials of different sizes,
the smaller particles sift between the larger
ones and tend to reduce bulkiness.

True Density
• It is the density of actual solid material devoid
of inter and intraparticle spaces or voids and is
defined as the ratio of the given mass of
powder and its true volume.
• It can be determined by two methods
1. Liquid displacement method
2. Gas or Helium Displacement method

Liquid Displacement Method
• It is used for non porous powders. Select the solvent in which
powder is insoluble. Normally water and ethyl alcohol are
used.
Wt of pycnometer= m1
Weight of pycnometer+ powder = m2
Weight of sample = m2-m1
Weight of pycnometer + sample + water = m3
Weight of pycnometer+ water = m4
Weight of water displaced by powder = m4-m3
True Density of Powder = weight of material
volume of water displaced by powder

Gas or Helium Displacement Method
• Helium penetrates the smallest pores and cervices. It gives a
very closer value to its true density.
Construction:
It consists of sample holder(A) which is sealed after introducing
the sample.
Valve (B) is connected to the sample holder. It has provisions for
removal of air and introduction of helium gas(since it does not
adsorb on the solid sample.
Pressure detector (C) is induced in order to maintain preset
constantpressure.
Piston (D) is attached to read the corresponding pressure which
is also related to volume of powder

Working:
Initially volume of empty pycnometer is determined
Air is removed from sample holder by applying vaccum
Helium is passed through valve B
Pressure is set at a particular value with a piston D
At this position the reading on scale denotes U1 which
is the vol of empty cell

In next step pycnometer is caliberated by placing a
standard sample(stainless steel spheres) of known
true volume in the sample holder
Sample holder is sealed and air is removed
Same amount of helium gas is introduced
Pressure is adjusted to preset value by piston
At this stage scale reading is denoted by U2
Difference between U1 and U2 gives the volume occupied by spheres

• Stainless steel spheres are now replaced by test
sample powder of known volume(Vc). Air is replaced
by helium gas.
• Pressure is adjusted with the help of a piston.
• At this stgae piston reading is denoted as Us.
• Difference between U1 and Us gives volume occupied
by sample.
• Where Vt is true volume of sample

Tests to evaluate the flowability of a powder:
1- Carr’s compressibility index
A volume of powder is filled into a graduated glass cylinder and repeatedly
tapped for a known duration. The volume of powder after tapping is
measured.
Carr’s index (%) =
T
apped density - Poured or bulk density x 100
Tapped density
Bulk density = weight / bulk volume
Tapped density = weight / true volume

Carr’s compressibility index (Cont.):
Relationship between powder flowability and % compressibility
Flow description % compressibility
Excellent flow 5 - 15
Good 16 - 18
Fair 19 - 21
Poor 22 - 35
Very poor 36 - 40
Extremely poor > 40

Tests to evaluate the flowability of a powder
(Cont.):
2- Hausner ratio:
Tapped density
Hausner ratio =
Poured or bulk density
Hausner ratio was related to interparticlefriction:
**Value less than 1.25 indicates good flow ( = 20% Carr ).
The powder with low interparticle friction, such as coarse spheres.
**Value greater than 1.5 indicates poor flow ( = 33% Carr ).
more cohesive, less free-flowing powders such as flakes.
**Between 1.25 and 1.5, added glidant normally improves flow.
** > 1.5 added glidant doesn’t improve flow.

Tests to evaluate the flowability of a powder
(Cont.):
can be
3- The angle of repose φ:
The frictional forces in a loose powder
measured by the angle of repose φ.
φ= the maximum angle possible between the surface
of a pile of powder and horizontal plane = coefficient
of friction μbetween the particles:
tan φ= μ
tan φ= h / r
r = d / 2

3- The angle of repose φ (Cont.):
- The sample is poured onto a horizontal surface and the angle of the
resulting pyramid is measured.
- The user normally selects the funnel orifice through which the powder
flows slowly and reasonablyconstantly.
Angle of repose less than 20 (excellent flow)
Angle of repose between 20-30 (good flow)
Angle of repose between 30-34 (Pass flow)
Angle of repose greater than 40 (poor flow)
***The rougher and more irregular the surface of the particles,
the higher will be the angle of repose.

Factors affecting the flow properties of
powders:
Improvement
of
Powder
Flowability
Particle’s
size
&
Distribution
Particle
Shape
& texture
Surface
forces
Flow
Activators

powders (Cont.):
Alteration of Particle’s size & Distribution
• There is certain particle size at which powder’s flow ability
is optimum.
Coarse particles are more preferred than fine ones as they are
less cohesive.
The size distribution can also be altered to improve
flowability by removing a proportion of the fine particle
fraction or by increasing the proportion of coarser particles,
such as occurs in granulation.

powders (Cont.):
Alteration of Particle Shape & texture
Particle’s Shape:
Generally, more spherical particles have better flow properties than
more irregular particles.
Spherical particles are obtained by spray drying, or by temperature
cycling crystallization.
Particle's texture:
particles with very rough surfaces will be more cohesive and have a
greater tendency to interlock than smooth surfaced particles.

powders (Cont.):
Formulation additives ( Flow activators)
- Flow activators are commonly referred as glidants.
-Flow activators improve the flowability of powders
by reducing adhesion and cohesion.
e.g. talc, maize starch and magnesium stearate

Micromeritics - Fundamental and Derived Properties of Powders

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