Micromeritics Particle Analysis Techniques

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Edited By: Jaytirmoy Barmon Micromeritics
Lecturer, Pharmacy, Varendra University
Micromeritics
Shahin Sarker
Lecturer
Department of Pharmacy
Jashore University of Science
and Technology (JUST)
Jaytirmoy Barmon Likhon
Lecturer
Varendra University, Rajshahi
Md Minhajul Islam
12th
Batch Student
Varendra University, Rajshahi
Micromeritics
Micromeritics is the science and technology of small particles. It is the study of a number of
characteristics, including particle size and size distribution, shape, angle of repose, porosity,
true volume, apparent density and bulkiness.
Important in pharmaceutical field:
The study of particle has a number of applications in the field of pharmacy which are given
below:
a) Drug release and dissolution:
Particle size and surface area influence the release of a drug from a dosage form that is
administered orally, rectally, parenterally, and topically. Higher surface area brings about
intimate contact of the drug with the dissolution fluids in vivo and increases the drug solubility
and dissolution.
b) Absorption and drug action:
Particle size and surface area influence the drug absorption and subsequently the therapeutic
action. Higher the dissolution faster the absorption. Hence quicker the drug action.
c) Physical stability:
Particle size influences the physical stability of suspensions and emulsions. Smaller the size
better is the physical stability (as it would take more time for particles to agglomerate)
d) Dose uniformity:
Particle size and shape also governs flow properties of powders and granules in tableting.
Powder with different particle size does not have uniformity of dose like tablet, capsule,
creams, ointments, suspensions, emulsions etc. (except solution).
Any interference in the flowability of powders or granules may alter the weight of the powder
blend and thus amount of drug incorporated into the tablet or capsules and thereby reduce the
uniformity of the dose.
Examples:
 Reduction of particles size improves surface area and can help in improving solubility
of certain drugs. e.g. The solubility of Griseofulvin can be greatly increased by particle
size reduction.
 Reduction of particles size can increase the rate of absorption of and consequently
bioavailability of many drugs e.g. tetracycline, aspirin, sulphonamides, nitrofurantoin
etc.

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Q. What are the fundamental properties & derived properties of powders?
Fundamental properties:
These properties relate to the individual particle.
The following are the five fundamental properties of collection of particles can be derived.
A. Particle size and size distribution.
B. Particle shape.
C. Particle volume.
D. Particle number.
E. Particle surface area.
Derived properties:
They are dependent on fundamental properties & define the factors relating to their
measurement.
A. Density of powders (a) bulk density (b) true density/tapped density
(c) granular density
B. Flow properties of powders
C. Porosity
D. Bulkiness
Q. What are the different means of expressing particle size?
Measurement for expressing particle size:
Particle size expressing is an indicating what sizes of particles are present in what proportions
in the sample particle group to be measured.
There are different means of expressing particle size e.g.
Unit Conversion in meter (m)
Millimeter (mm) 1 mm = 10-3
m
Micrometer (µm) 1 µm = 10-6
m
Nanometer (nm) 1 nm = 10-9
m
Picometer (pm) 1 pm = 10-12
m
Femtometre (fm) 1 fm = 10-15
m
Q. Describe the method or technique of particle size distribution or size analysis?
Particle size distribution:
When the number or weight of particles lying within a certain size range is plotted against the
size range or mean particle size, a so-called frequency distribution curve is obtained. This is
important because it is possible to have two samples with the same average diameter but
different distributions. The following techniques/methods are generally used for particle size
determination (PSD):
A. Microscopic Technique (Range: 0.2–100 μm).
B. Sieving Technique (Range: 40–9500 μm).
C. Sedimentation Technique (Range: 0.08–300 μm).
D. Conductivity Method (Range: 0.5–500 μm).

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A. Microscopic Technique:
o Microscopy is the technique used to view objects that cannot be seen by the naked eye.
o Particle size in the range of 0.2 – 100 μm can be measured.
o This method gives number distribution which can be converted to weight distribution
o Optical microscope lens has limited resolving power.
o Advanced microscopes have better resolving power and can measure size in nano
range: Ultramicroscope, Electron microscope- Scanning Electron microscope (SEM),
Transmission Electron microscope (TEM).
Method description:
Procedure:
 Eye piece of the microscope is fitted with a micrometer.
 This eye-piece micrometer is calibrated using a standard stage micrometer.
 The powder sample is dispersed in a suitable vehicle in which it does not dissolve and
its properties are not altered. (e.g. water, paraffin oil.)
 This sample is mounted on a slide and placed on the stage under the objective of
microscope.
Special notes:
At least 300-500 of particles that must be counted to obtain a good estimation & data
analysis.
In general around 625 particles are visualized. Their diameter is noted and mean is
computed.
Application: Particle size analysis in suspensions, aerosols, globule size analysis in
emulsion
Advantages
 One can view particles
 Any aggregates detected
 Contamination of particles detected
 Use of cover slip for arresting motion of particles
 Easy and simple

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Disadvantages
 Length and breadth can be detected but depth or thickness of particles cannot be
measured
 Slow, time consuming, tedious, inaccurate
 Number of particles to be measured is more
 Large sample required
B. Sieving Technique
o Sieving method is an ordinary and simple method.
o Sieving is defined as a method in which two or more components of different sizes are
separated from a mixture on the basis of the difference in their sizes.
o It is widely used as a method for the particle size analysis
o Sieve analysis is usually carried out using dry powders. Although, for powders in liquid
suspension or which agglomerate during dry sieving, a process of wet sieving can be
used.
o Sieving method directly gives weight distribution.
o It find application in dosage form development of tablets and capsules.
o Normally, 15% of fine powder should be present in granulated material to get proper
flow of material and achieve good compaction.
o Thus percent of coarse, moderate, fine powder is estimated by this method.
Method description:
Theory & Apparatus:
 Sieve analysis utilizes a wire mesh made of brass, bronze or stainless steel with known
aperture (hole) diameters which form a physical barrier to particles.
 The standard sieve sizes are as per the pharmacopoeia
 Most sieve analyses utilize a series, stack (layer) of sieves which have the coarser mesh
at the top of the series and smallest mesh at the bottom above a collector tray (The mesh
size goes on decreasing from top to bottom)
 A sieve stack usually comprises 6-8 sieves.

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Procedure:
 Powder is loaded on to the coarsest sieve of the stack and then it is subjected to
mechanical vibration for specified time, e.g. 20 minutes.
 After this time, the powder retained on each sieve is weighed
 The particles are considered to be retained on the sieve mesh with an aperture
corresponding to the sieve diameter.
 The size is estimated as per the standards given in pharmacopoeia
Precaution:
Care should be taken to get reproducible results.
The type of motion, time of operation, speed and weight of powder should be fixed and
standardized.
Advantages:
 Most widely used method for measuring particle size.
 It is inexpensive, simple and rapid.
 Generally useful for course particle.
 Give reproducible results if parameters are standardized
Disadvantages:
 The particle may aggregate during sieving due to generation to electrostatic charge.
 Moisture can also lead to aggregation of powder and actual particle size may not be
obtained.
 Sieve loading and duration of mechanical shaking can influence the result.
 Attrition between particles during the process may cause size reduction giving
inaccurate results.

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Example Math-I: Suppose 250 gm of materials is passed through sieving technique and 120
gm, 80 gm, 50 gm materials is retained in sieve-1, sieve-2 and sieve-3 respectively. Calculate
the percentage of materials retained in each sieve.
We know,
Percentage of materials retained in a single sieve = (Retained quantity ÷ Total quantity) × 100
Sieve-1: (120 gm ÷ 250 gm) × 100 = 48 %
Sieve-2: (80 gm ÷ 250 gm) × 100 = 32 %
Sieve-3: (50 gm ÷ 250 gm) × 100 = 20 %
Practice Math-01: Suppose 715 gm of materials is passed through sieving technique and 350
gm, 200 gm, 165 gm materials is retained in sieve-1, sieve-2 and sieve-3 respectively. Calculate
the percentage of materials retained in each sieve.
gm, 500 gm, 375 gm, 125 gm materials is retained in sieve-1, sieve-2, seive-3 and sieve-4
respectively. Calculate the percentage of materials retained in each sieve.
gm, 170 gm, 70 gm 95 gm, 345 gm materials is retained in sieve-1, sieve-2, seive-3, seive-4
and sieve-5 respectively. Calculate the percentage of materials retained in each sieve.
C. Sedimentation Technique:
In this method particle size can be determined by examining the powder as it sediments out.
Description:
Sample preparation:
o Powder is dispersed in a suitable solvent.
o If the powder is hydrophobic, it may be necessary to add dispersing agent to aid wetting
of the powder.
o In case where the powder is soluble in water it will be necessary to use non- aqueous
liquids or carry out the analysis in a gas.
Principle of Measurement
 Particle size analysis by sedimentation method can be divided into two main categories
according to the method of measurement used.
 One of the type is based on measurement of particle in a retention zone. Another type
uses a non-retention measurement zone.
 Here we will discuss only non-retention zone measurement. An example of a non-
retention zone measurement is known as the pipette method.
Andreasen pipette method:
 One of the most popular of the pipette methods was that developed by Andreasen and
Lundberg and commonly called the Andreasen pipette.
 In this method, known volumes of suspension are drawn off and the concentration
differences are measured with respect to time.
 It involves measuring the % of solids that settle with time in a graduated vessel.

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Construction:
■ The Andreasen fixed-position pipette consists of a 200 mm graduated cylinder which
can hold about 500 ml of suspension fluid.
■ A pipette is located centrally in the cylinder and is held in position by a ground glass
stopper so that its tip coincides with the zero level.
■ A three way tap allows fluid to be drawn into a 10 ml reservoir which can then be
emptied into a beaker or centrifuge tube.
Method:
 A 1% suspension of the powder in a suitable liquid medium is placed in the pipette.
 At a given intervals of time, samples are withdrawn from a specified depth without
disturbing the suspension.
 The amount of powder can be determined by weight following drying or centrifuging;
alternatively, chemical analysis of the particles can be carried out.
 The particle size is determined in terms of stokes’ diameter (the diameter of a particle
measured during sedimentation at constant rate) using modified Stokes' equation.
Here,
dst: stokes’ diameter
n: viscosity of medium
h: sedimentation height
ps- pf: difference in density of particle and fluid
Fg: force of gravity
t: sedimentation time
 A pipette is located centrally in the cylinder and is held in position by a ground glass
stopper so that its tip coincides with the zero level.
 A three way tap allows fluid to be drawn into a 10 ml reservoir which can then be
emptied into a beaker or centrifuge tube.
 The amount of powder can be determined by weight following drying or centrifuging.
 The data of cumulative weight is used for the determination of particle weight
distribution, number distribution etc..

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Advantages:
 The apparatus is inexpensive and the technique is simple.
 The results obtained are precise provided the technique is adequately standardized.
Disadvantages:
 The method is laborious since separate analyses are required for each experimental
point on the distribution curve.
 Very small particle cannot be determine accurately since their setting is unduly prolong
and is subjected to interference due to convection, diffusion and Brownian motion.
Example Math-II: A sample of powdered zinc oxide, density 5.60 g/cm3
is allowed to settle
under the acceleration of gravity, 981 cm/sec2
at 25°C. The rate of settling v is 7.30 × 10-3
cm/sec the density of the medium is 1.01 g/cm3
and its viscosity is 1 centipoise = 0.01 poise or
0.01 g/cm sec. Calculate the Stokes diameter of the zinc oxide powder.
Solution:
We know, Stokes law,
Practice Math-04: A sample of powdered aluminium oxide, density 3.95 g/cm3
is allowed to
settle under the acceleration of gravity, 981 cm/sec2
. The rate of settling v is 6.17 × 10-3
cm/sec
the density of the medium is 1.06 g/cm3
and its viscosity is 1 centipoise = 0.01 poise or 0.01
g/cm sec. Calculate the Stokes diameter of the aluminium oxide powder.
Practice Math-05: A sample of powdered CaCO3, density 2.71 g/cm3
is allowed to settle under
the acceleration of gravity, 981 cm/sec2
at 25°C. The rate of settling v is 3.58 × 10-3
cm/sec the
density of the medium is 1.03 g/cm3
and its viscosity is 1 centipoise = 0.01 poise or 0.01 g/cm
sec. Calculate the Stokes diameter of the CaCO3 powder.
D. Conductivity Method:
There are various subtypes. Two popular methods are-
i. Electrical stream sensing zone method (Coulter counter)
ii. Laser light scattering methods:
It is based on the principle of change in light intensity. The measurement of this change in light
intensity gives estimate of particle size.
Electrical stream sensing zone method (Coulter counter)
Sample Preparation:
o Powder samples are dispersed in an electrolyte to form a very dilute suspension.
o The suspension is usually subjected to ultrasonic agitation to break up any particle
agglomerates.
o A dispersant may also be added to aid particle deagglomeration.

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Apparatus & Method:
A coulter counter is an apparatus for counting and sizing particles suspended in electrolytes. It
consists of two electrode one of them whose is dipped into a beaker the other electrode is dipped
into the electrolytic solution contained in a glass tube the glass tube has a very small artifice at
its lower in through the particle are shake into the inner glass tube.
A known volume of the suspension is pumped through the orifice. So that only one particle
passes at a time. As the particle passes through the orifice. The orifice electrical resistance
increase. Electrical resistance is directly proportional to the volume of the particle. By
measuring determine the volume of the particle.
Advantages:
 Very rapid operation a single count packing
less than 30 sec.
 The more reliable result since a large number
are counting particle.
 Since the apparatus is automatic, operator
variability is avoided.
Disadvantages:
 Aggregation of a particle can forgive results.
 The material has to be suspended in an
electrolytic before measurement.

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Particle Shape:
Particle shape also has influence
on surface area, flow properties,
packing and compaction of the
particles. Spherical particles
have minimum surface area and
better flow properties. The more
asymmetric a particle, the
greater is the surface area per
unit volume. Shape can also
have influence on rate of
dissolution of drugs.
Surface area
The surface area of a solid object is a measure of the total area that the surface of the object
occupies.
Specific surface area i.e. surface area per unit weight (Sw) or unit volume (Sv) can be
estimated as follows:
Sv = surface area of particles ÷ volume of particles
Sv = (number of particles × surface area of each particle) ÷ (number of particles × volume of
each particle)
Surface area is an important parameter as the bioavailability of certain drugs is dependent on
surface area. e.g. Bephenium (anthelminitic), Griseofulvin (antifungal) - if the surface area is
less than specified, the absorption decreases.
Derived properties of powders
Porosity of powder:
Porosity is defined as the ratio of the total pore volume to the apparent volume of the particle
or powder.
Suppose a powder, such as zinc oxide, is placed in a graduated cylinder and the total volume
is noted. The volume occupied is known as the bulk volume, Vb. If the powder is nonporous,
that is, has no internal pores or capillary spaces, the bulk volume of the powder consists of
the true volume of the solid particles plus the volume of the spaces between the particles.
The volume of the spaces, known as the void volume, v, is given by the equation:
Void volume, V = Vb – Vp
Where Vp is the true volume of the particles.
The porosity or voids € of the powder is defined as the ratio of the void volume to the bulk
volume.

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Porosity,
€ =
V
𝑉𝑏
€ =
Vb − Vp
Vb
€ = 1 −
𝑉𝑝
𝑉𝑏
Density of powder:
The density of powder defines the mass per unit volume of the powder.
Type of density:
a. Bulk density.
b. True density.
c. Granule density.
Before tapping
After tapping
a. Bulk density: Bulk density is defined as the ratio of the mass of powder to the bulk volume
of powder. Bulk density is denoted by ρb.
ρb =
Mass of powder
Bulk volume of powder
ρb =
m
𝑉b
b. True density/Tapped density: True density is defined as ratio of the mass of powder and
its true volume. True density is denoted by ρt.
ρt =
Mass of powder
True volume
ρt =
m
vt

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c. Granule density: Granule density is defined as the ratio of granular powder to the volume
of the granule. Granule density is denoted by ρg.
ρg =
Mass of granules
Volume of Granules
ρg =
mg
Vg
Applications
i. Decides the size of the capsule based on bulk and tapped volume of a given sample -
Higher the bulk volume, lower the bulk density and bigger the size of the capsule.
ii. Helps to decide proper size of a container or packing material.
Bulkiness:
The reciprocal of bulk density is known as bulkiness.
Bulkiness =
Bulk volume
Mass of powder
=
Vb
m
Q. How can you determine the true density of the powder?
Liquid displacement method:
In this method a liquid in which the solid is insoluble in generally used. The powder whose
density is to be determined is added into a standard flask of known volume and the weight
determine. An ordinarypycnometer is suitable for this purpose. Now, a liquid which the powder
insoluble is introduced into the pycnometer. The liquid fills up to the void space between the
particles until the hold volume of the pycnometer occupied. The pycnometer is again weighted.
The contents of the pycnometer are emptied and only the liquid is filled into it and weighted.
The true density of is obtained as the ratio between the weight of the material and the weight
of the liquid is displaced.
Wt. of pycnometer: w1
Wt. of pycnometer +
sample: w2
Sample wt.:
w3= w2-w1
Wt. of pycnometer +
sample + solvent: w4
Wt. of liquid displaced
by sample:
w5 = w4-w2
Thus, true density
= w3/ w5
Limitations:
For non-porous powders only. In case of porous powders need Helium displacement method.

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Flow properties of powder:
The specific properties of a powder that affect its flow are known as flow properties. Examples
of flow properties include bulk density, permeability, and cohesive strength. The flow property
of powder is an important parameter to be considered in the production of the pharmaceutical
dosage form. Such as tablet, capsule etc.
The poor flow of powder due to the reasons:
i. Cohesiveness or stickiness between particle due to the presence of van der Waals force,
surface tension and electrostatic force.
ii. Adhesion between particles at the container wall due to the above force.
iii. Friction between the particles due to the surface roughness.
iv. The physical interlocking of the particle due to their irregular shape.
v. Presence of moister causes for poor flow of powders.
Due to the poor flow there are also some bad effect on pharmaceutical dosage form. These are:
i. Tablet weight variation in the dosage.
ii. Segregation of granules.
iii. Demixing may take place which causes: a. Color variation b. Variation of therapeutic
effect.
Q. Describe the different tests to evaluate the flowability of a powder?
A. Housner ratio.
B. Carr's compressibility index.
C. The angle of repose.
A. Housner ratio:
The Hauser ratio is a number that is correlated to the flow ability of a powder or granular
material. The Hauser ratio is calculated by the formula,
H =
ρT
ρB
Where,
ρT is the tapped density of the powder.
ρB is the bulk density of the powder.
Bulk density =
Weight
Bulk volume
Tapped density =
Weight
Tapped volume
So, we can write,
Housner ratio =
Bulk volume
Tapped volume

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B. Carr's compressibility index:
The Carr index is an indication of the compressibility of a powder. The Carr index is
calculated by the formula,
Carr's compressibility index (%) =
Tapped density−Bulk density
Tapped density
× 100
C =
ρT− ρB
ρT
× 100
Where,
ρT is the tapped density of the powder.
ρB is the bulk density of the powder.
Example Math-III: If a material weight 371 mg and bulk volume 121 ml in a cylinder. The
material is subjected to 50 times tapping and volume observed after tapping is 113 ml. Calculate
the Hausner ratio and Carr’s compressibility index including comment about flow ability.
Given that,
Weight = 371 mg
Bulk volume = 121 ml
Tapped volume = 113 ml
Housner ratio =?
Carr’s compressibility index (%) =?
We know,
Bulk density =
Weight
Bulk volume
=
371 mg
121 ml
= 3.06 mg/ml
Tapped density =
Weight
Tapped volume
=
371 mg
113 ml
= 3.28 mg/ml
Hence,
Housner ratio =
Tapped density
Bulk density

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=
3.28 mg/ml
3.06 mg/ml
= 1.07
Result: Housner ratio 1.07
Comment: Excellent flow
Now, Carr's compressibility index (%) =
Tapped density−Bulk density
Tapped density
× 100
=
(3.28−3.06) mg/ml
3.28 mg/ml
× 100
= 6.70 %
Result: Carr's compressibility index 6.70 %
Comment: Excellent flow
Practice Math-06: If a material weight 275 mg and bulk volume 89 ml in a cylinder. The
Practice Math-07: If a material weight 401 mg and bulk volume 156 ml in a cylinder. The
C. The angle of repose:
It is defined as the maximum angle possible between the surface of a pile of the powder and
the horizontal plane. It is an indication of the resistance to flow of the powder.
The Angle of repose is calculated by the formula,
tan 𝛼 =
h
r
Where,
α = Angle of repose
h = Height of powder concentration
r = Radius of powder concentration
Remember one thing, r =
d
2
(where, d is the diameter)

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Example Math-IV: If height of a powder cone is 2.5 m and diameter 600 cm, calculate the
angle of repose and comment about flow properties of that powder.
Given that,
Hight = 2.5 m
Diameter, d = 600 cm
= 6 m [1 meter = 100 cm]
Angle of repose = ?
We know,
Radious, r =
d
2
=
6 m
2
= 3 m
So, Angle of repose,
tanѲ =
h
r
Ѳ = tan−1
(
h
r
)
Ѳ = tan−1
(
2.5
3
)
Ѳ = tan−1
(0.83)
Ѳ = 39.69°
Result: Angle of repose 39.69°
Comment: Fair flow
Practice Math-08: If height of a powder cone is 4.5 m and diameter 900 cm, calculate the
angle of repose and comment about flow properties of that powder.
Practice Math-09: If height of a powder cone is 1.5 m and radius 3.7 m, calculate the angle of
repose and comment about flow properties of that powder.
Practice Math-10: If height of a powder cone is 4.6 m and radius 2.3 m, calculate the angle of
repose and comment about flow properties of that powder.

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Factors affecting the flow properties of powder.
Related questions:
Q. How can you improve the flow properties of a powder?
Flow properties of powders can be improved by one or more of the following methods-
i. Altering the particle size:
Increasing the average particle size of particles improves the flow properties due to reduction
in the cohesive forces. During tableting, fine powders are converted to course granules in order
to impart good flow properties to them.
ii. Removal or addition of fines:
Presence of small proportion of fines in a powder or granular mass may improve the flow
properties by filling up the pits and crevices on the surface of the particle. On the other hand,
larger proportion of fines may retard the flow properties. So, an optimum concentration of fines
is desirable for best results.
iii. Altering the particle shape and texture:
Spherical particles tend to better flowability as compared to irregular particles. Hence
techniques like spray drying may be used to give spherical particles with good flow properties.
Alteration of crystallization conditions may also produce particles of desired shape and texture.
iv. Altering surface forces:
Reduction of electrostatically charges on particle surface by reducing the frictional contents
such as during transfer or during process (e.g. sieving) can improve the flow properties.
v. Removing the extra moisture:
Drying of powders in order to remove moisture from surface can improve the flow properties
by decreasing the cohesiveness.
vii. Adding lubricants or glidants:
Flow properties of pharmaceutical powders may be improved significantly by the addition of
materials which known as lubricants or glidants. They improve flow flowability of powders
reducing adhesion and cohesion. For example: magnesium stearate, talc, starch etc.
Note:
Lubricants- reduce friction between surfaces in mutual contact
Glidants- reduce interparticular friction.

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