Unit IV Micromeretics

S.Y.B.PHARM
Div. B
Subject: Physical Pharmaceutics-I
UNIT- III
MICROMERITICS
1

STUDY OF PARTICLES
PARTICLE
SHAPE
PARTICLE
SURFACE
AREA
PARTICLE
WEIGHT
PARTICLE
NUMBER
PARTICLE
SIZE
PARTICLE
PARTICLE SIZE
DISTRIBUTION
PARTICLE
VOLUME
2

MICROMERITICS ➢ The term micromeritics was given to the science and
technology of small particles by J. M. Dalla Valle.
➢ It is thus the study of the fundamental and derived
properties of individual as well as a collection of
particles.
➢The unit of particle size used most frequently in
micromeritics is the micrometer, µm, also called the
micron, µ.
1 µm = 10-6 m
1 µm = 10-4 cm, and
1 µm = 10-3 mm
1 µm = 1000 nm
3

2. Absorption and drug action
➢ Particle size and surface area influence the drug
absorption and subsequently the therapeutic
action.
➢ Smaller the Particle size greater the surface area
and hence Higher the dissolution, faster the
absorption and hence quicker and greater the drug
therapeutic action.
APPLICATIONS
1. Release and dissolution
➢ Particle size is inversely proportional to surface area
➢ As particle size decreases , surface area increases
➢ 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 in vivo and increases the
drug solubility and dissolution.
3. Physical stability
➢ The particle size in a
formulation influences the
physical stability of the
suspensions and emulsions.
➢ Such as physical stability of
the suspensions and
emulsions depends upon
size of dispersed material.
➢ Smaller the size of the
particle, better the physical
stability of the dosage
form.
4

4. Dose uniformity
➢ Good flow properties of granules and powders are
important in the manufacturing of tablets and
capsules.
➢ Some of the reasons for producing free-flowing
pharmaceutical powders include:
1. Uniform feed from bulk storage containers or
hoppers into the feed mechanisms of tabletting or
capsule-filling equipment, allowing uniform particle
packing and a constant volume-to-mass ratio which
maintains tablet weight uniformity.
2. Uneven powder flow can result in excess entrapped air
within powders.
3. Uneven powder flow can result from excess fine
particles in a powder, which increase particle-die-wall
friction, and increase dust contamination risks during
powder transfer.
5

Properties of Powders
A. Fundamental properties
1. Particle size and size
distribution
2. Particle shape
3. Particle surface area
4. Particle weight
5. Particle number
6
1. Fundamental properties :-These properties relate to the individual particle.
2. Derived properties :- They are dependent on fundamental properties & define the factors
relating to their measurement.
B. Derived properties
1. Density of powders
(a). Bulk density
(b). Tapped density
2. Flow properties of powders
3. Porosity
4. Bulkiness

1. Particle Size and Size Distribution
❑If same size particles are present in particular dispersion then
the system is called as Monodisperse.
❑If different size particles are present in particular dispersion
then the system is called as Polydisperse.
❑Two properties are important, namely,
(a) The shape and surface area of the individual particles and
(b) The size range and number or weight of particles present
and, hence, the total surface area.
7

2. Average Particle Size & Size distribution
10

United States Pharmacopeia
General Chapters: <811> POWDER FINENESS
Classification of Powders by Fineness
Classification of Powder d50 Sieve Opening (µm)
Very Coarse > 1000
Coarse 355–1000
Moderately Fine 180–355
Fine 125–180
Very Fine 90–125
d50= smallest sieve opening through which 50% or more of the material passes
PARTICLE SIZES AS PER USP :
11

*Methods
used to
determine
/measure
particle
size of a
powder;
1. Optical Microscope
method
2. Sieve methods
3. Sedimentation
methods
4. Conductivity method
(Coulter counter Method)
12

1.Optical
Microscope
methods
Advantage:
1. Microscopy allows the observer to view the particles.
2. Agglomeration of particles & any contamination in the
powder can be easily detected.
3. While counting particles in the dispersion, it must be free
from motion. This can be avoided by mounting the sample
with a cover slip.
4. Easy & Simple
Disadvantage:
1. The diameter is obtained from only two dimensions of the
particle; depth of the particle is not measured.
2. The number of particles that must be counted (300-500) to
obtain a good estimation of the distribution makes the
method somewhat slow and tedious.
Size Range: By this method particle size in
the range of 0.2-100 µm can be measured.
This method is used to determine;
a) Particle size analysis in suspensions
b) Globule size analysis in emulsions
c) Particle size analysis in aerosols 13

1.Eye piece of the microscope is
fitted with a micrometer.
2. This eye-piece micrometer is
calibrated using a standard stage
micrometer.
3. The powder sample is dispersed
in a suitable vehicle in which it
does not dissolve and its
properties are not altered. (eg.
water, paraffin oil.) 4. This sample
is mounted on a slide and placed
on the stage under the objective of
microscope
14

METHOD :
1. According to the optical microscopic method, the
eyepiece of microscope is fitted with a micrometer.
2. It is then calibrated using standard stage micrometer.
3. Take the powder sample & prepare a suspension with
suitable vehicle such as paraffin oil.
4. When water is used as a vehicle then verify the aspect of
hydration ie swelling of the particles.
5. The sample of an emulsion or suspension is mounted on
ruled slide on a mechanical stage
6. The size of the particles is estimated with the help of
eyepiece micrometer.
7. The number of particles that must be counted are in the
range from 300-500 to estimate the true mean.
16

• In this method, the particle size is expressed as
Following diameters that can be measured;
1. Martin's diameter (M)
The length of the line which bisects the particle
image. The lines may be drawn in any direction
which must be maintained constant for all image
measurements.
2. Feret's diameter (F)
is the distance between two tangents on opposite
sides of the particle, parallel to some fixed
direction.
3. Projected area diameter (da or dp)
is the diameter of a circle having the same area as
the particle viewed normally to the plane surface
on which the particle is at rest in a stable position.
17

2. Sieve methods
• Size Range: Particles having size range between 50-1500 µm can be measured
by this method.
• In this method the particle size is expressed as dsieve ie sieve diameter; which
describes diameter of a sphere that passes through the sieve aperture as the
asymmetric particle.
• Method:
1. Standard sieves of different mesh numbers ae available commercially as per the
specifications of IP & USP to cover a wide range of size.
2. Mesh number: Number of openings per inch
3. These sieves are designed to sit in a stack so that material falls through smaller
and smaller meshes until it reaches a mesh which is too fine for it to pass
through.
4. A powder sample is placed on the top sieve.
5. The stack of sieves is mechanically shaken for a certain period of time to promote
the passage of the solids.
6. The powder retained on each sieve is weighed.
7. Also, The fraction of the material between pairs of sieve sizes is determined by
weighing the residue on each sieve & it is expressed in terms of arithmetic means
of two sieves.
18

19
Method:
➢ 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)

20
Method:
• A sieve stack usually comprises 6-8 sieves.
• Powder is loaded on to the coarsest sieve of
the stack and then it is subjected to
mechanical vibration for specified time, eg
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

Advantage:
1. It is inexpensive, simple & rapid method.
2. Results are reproducible
Disadvantage:
1. Lower limit of the particle size is 50 µm.
2. If powder is not completely dry, the apertures become clogged with the
particles leading to improper sieving.
3. During shaking, attrition may occur ie particles may get colloid with each
other causing size reduction of particles. This leads to errors in estimation.
Application:
• This method has application in dosage form development of tablets &
capsules.
• Normally 15% of fine powder that passed through 100 mesh should be
present in granulated material to get a proper flow of material & to
achieve good compaction in tabletting. Thererfore % of fine or coarse
powder can be quickly estimated by this method. 21

3. Sedimentation
Method
• Size Range :
1. Particles having size range between 1-200 µm can be measured by this method.
2. In this method the particle size is expressed as, Stokes diameter, dst, is the diameter
which describes an equivalent sphere undergoing sedimentation at the same rate as
the asymmetric particle.
3. Sedimentation of particles is evaluated by Anderson pipette method.
4. It is usually consist of 550 ml cylindrical vessel containing a 10 ml pipette sealed to a
glass stopper.
5. When the pipette is placed into the cylinder its lower tip is 20 cm below the surface
of the suspension.
• Procedure :
1. Prepare 1 or 2% suspension of the powder in a suitable vehicle.
2. Add a deflocculating agent- it will help in uniform dispersion of the suspension.
3. Transfer the suspension into Anderson vessel.
4. Place the glass stopper & shake the vessel to distribute the suspension uniformly.
5. Remove the stopper & place the two-way pipette & securely suspend the vessel in a
constant temperature water bath. 22

6. At different time intervals 10 ml samples are withdrawn using two-way stopcock &
collected in watch glass.
7. Samples are then evaporated & weighed. The weight of the particles obtained in
each time interval is taken & from that particle size distribution is determined.
8. Now, particle diameter is calculated from Stoke’s law.
Vm: rate or velocity of settling of particles in suspension or emulsion
h : distance of fall in time t: Height of the liquid above the lower end of the pipette
at the time of withdrawing the samples
ρs: density of particle
ρf: density of dispersion fluid medium
g : acceleration due to gravity
η : viscosity of medium
dsph: Stokes diameter
• This equation holds good for spheres falling freely at constant rate without
hindrance. Here it is assumed that the rate or velocity of settling of particles is
same as the sphere & hence particle size is expressed as the size of an equivalent
sphere
( )




18
2
sph
f
s gd
−
= 𝑑𝑠𝑝ℎ =
18𝜂
𝜌𝑠 − 𝜌𝑓 𝑔
𝑥
𝑡
23

24
Method:
• In this method particle size can be
determined by examining the powder as it
sediments out.
Sample preparation:
✓ Powder is dispersed in a suitable solvent.
✓ If the powder is hydrophobic, it may be
necessary to add dispersing agent to aid
wetting of the powder.
✓ 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.
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.

• When the powder is suspended in a vehicle, initially the particles of large diameter settle
down due to heavy weight.
• After some time, particles of intermediate diameter will settle.
• Finally, the particles of smaller size settle.
• Hence the study involves the sampling during sedimentation at different time intervals.
Applications: Sedimentation method finds Applications in;
1. Formulation & evaluation in suspensions
2. Formulation & evaluation in emulsions
3. Determination of molecular weight of polymers
4. Physical stability of suspension depends on rate of settling of particles in a suspension or
other dosage form 25

Advantages :
• Equipment required can be relatively simple and inexpensive.
• Can measure a wide range of sizes with considerable accuracy and
reproducibility.
Disadvantages :
• Sedimentation analyses must be carried out at concentrations which are
sufficiently low for interactive effects between particles to be negligible
so that their terminal falling velocities can be taken as equal to those of
isolated particles.
• Large particles create turbulence, are slowed and are recorded undersize.
• Particles have to be completely insoluble in the suspending liquid.
26

4.Conductivity
method (Coulter
counter Method)
• This method is used for particle volume
measurement.
• Particle volume is measured & converted into
particle diameter.
• As this Instrument measures particle volume
which can be expressed as dv ie Volume
diameter : the diameter of a sphere that has
the same volume as that of asymmetric
particle.
• Size Range: Particles having size range between
0.5 -200 µm can be measured by this method.
27

Method:
• In this type of machine the powder is suspended in an electrolyte
solution for eg Sodium chloride solution
• Sample Preparation:
1. Powder samples are dispersed in an electrolyte to form a very dilute
suspension.
2. The suspension is usually subjected to ultrasonic agitation to break
up any particle agglomerates.
3. A dispersant may also be added to aid particle deagglomeration.
28

• This suspension is then filled in
sample cell, that has an orifice &
maintains the contact with
external medium.
• Electrodes are placed in the
solution; positive electrode inside
the cell & negative outside the cell.
• A constant voltage is applied
across the electrodes. In this
position current passes.
• When the suspended particles
passes through an orifice, it
displaces its own volume of
electrolyte into the beaker.
• The net result is change in
electrical resistance.
• This change in electrical
resistance is termed as particle
volume.
29

Advantages:
• Using coulter counter apparatus
approximately 4000 particles per second can
be counted.
• Therefore size distribution analysis can be
completed in relatively short period of time.
• Also it gives accurate results.
Disadvantages:
• This method is not suitable for polar & highly
water soluble materials due to solvation.
• In such cases if a non solvent is used to
suspend the particles it may not produce
adequate conductance.
• Expensive
Conductivity method is also known as
Electrical stream sensing zone method
because fluid suspension of particles
passes through a sensing zone in which
individual particles are electronically
sized, counted & measured.
30

31
Particle Shape Determination:
➢ 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.
➢ Shape can also have influence on rate of
dissolution of drugs.
➢ Techniques of determination are:
a) Microscopy (refer in particle size
determination)
b) Light scattering
Particle Shape

32
Particle Surface Area
Surface Area Determination
1. Adsorption
method
2. Air Permeability
method

33
1. Adsorption method:
a) Surface area is most commonly determined based on Brunauer-Emmett-
Teller (BET) theory of adsorption.
b) Most substances adsorb a monomolecular layer of gas under certain
conditions of partial pressure of gas and temperature. The adsorption
process is carried out at liquid nitrogen temperatures -196˚C.
c) Once surface adsorption has reached equilibrium, the sample is heated at
RT and Nitrogen gas is desorbed. Its volume is measured.
d) As each N2 mol. occupies fixed area, one can compute surface area of pre-
weighed sample.

34
2. Air Permeability method:
a) Powder is packed in sample holder
b) Packing appears as series of capillaries
c) Air is allowed to pass through the capillaries
at constant pressure
d) Resistance is created as air passes through
capillaries thus causing pressure drop.
e) Greater the surface area greater the
resistance
f) Air permeability is inversely proportional to
the surface area

36
(a). Bulk density
(b). Tapped density
2. Flow properties of
powders
3. Porosity
4. Bulkiness
➢ Density is defined as weight (Mass) per unit
volume (W/V).
➢ During tapping, particles gradually pack
more efficiently, the powder volume
decreases and the tapped density increases.

37
(a). Bulk density: The bulk density value includes the volume
of all of the pores within the powder sample.
Weighed amount of powder was placed in 100 ml
measuring cylinder. Volume occupied by the powder
without disturbing the cylinder was noted down as bulk
volume (v0)
(b). Tapped density: The true density or absolute density of a
sample excludes the volume of the pores and voids within
the powder sample.
The cylinder was fitted into bulk and tapped
density apparatus and 500 taps were performed. After
500 taps, the volume was noted down as vT.

38
2. Powder flow properties
➢ P’ceutical powders may be broadly classified as free-flowing or cohesive.
➢ Most flow properties are significantly affected by changes in particle size, density,
electrostatic charges, adsorbed moisture.
➢ Good flow property is required for easy and uniform flow from hopper to die cavity
ensuring accurate weight and dose.
➢ The flow properties of powders are estimated by measuring following 3 parameters;
a) Angle of repose
b) % compressibility (Carr’s index)
c) Hausner’s ratio

39
(a). The angle of repose () :
✓ Fixed height funnel method is used to determine angle of repose
in which funnel was adjusted such that the stem of the funnel lies
2 cm above the horizontal surface.
✓ The drug powder is allowed to flow from the funnel under the
gravitational force till the tip of the pile just touched the tip of
the funnel.
✓ The diameter of the pile is determined by drawing a boundary
along the circumference of the pile.
✓ Experiment is performed in triplicate to calculate average
diameter.
✓ Values of height and radius are taken & substituted in the
equation and angle of repose is calculated.
It is defined as the maximum angle possible between the
surface of a pile of the powder & the horizontal plane

41
(a). % compressibility (Carr’s 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 measure.
Tapped density - Bulk density
Carr’s index (%)= Tapped density
Table: 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
X 100

42
(C). Hausner’s ratio
Tapped density
Hausner ratio =
Poured or bulk density
➢ Hausner ratio was related to interparticle friction:
➢ Value less than 1.25 indicates good flow (=20% Carr).
➢ Value greater than 1.5 indicates poor flow (= 33% Carr’s Compressibility
Index)).
➢ Between 1.25 and 1.5 added glidant normally improves flow.
➢  1.5 added glidant doesn’t improve flow.
➢ Glidants are the substances that are added to improve the flow of a powders.
➢ A glidant will only work at a certain range of concentrations. Above a certain
concentration, the glidant will in fact function to inhibit flowability.
➢ In tablet manufacture, glidants are usually added just prior to compression.
➢ Examples of glidants include magnesium stearate, Aerosil (colloidal silicon
dioxide), starch and talc.

43
➢ Porosity definition: It is the ratio of the
volume of voids between particles, plus the
volume of pores, to the total volume
occupied by the powder, including voids and
pores.
➢ A set of particles can be filled into a volume
of space in different ways.
➢ This is because by slight vibration, particles
can be mobilized and can occupy a different
spatial volume than before.
➢ This changes the bulk volume because of
rearrangement of the packing geometry of
3. Porosity (Packing Properties)
Example:
➢ A set of monosized spherical particles can be
arranged in many different geometric configurations.
➢ In Fig. a, when the spheres form a cubic
arrangement, the particles are most loosely packed
and have a porosity of 48%.
➢ In Fig.b, when the spheres form a rhombohedral
arrangement, they are most densely packed and
have a porosity of only 26%.
➢ The porosity used to characterize packing geometry
is linked to the bulk density of the powder.

44
➢ Porosity is also defined as a Void
volume (v) ie the volume of space
➢ Formula for Void Volume:
V = Vb-Vt
Where Vb= Bulk Volume
Vt= True Volume
Formula for porosity:
ε = Vb – Vt
Vb
➢ Thus bulk density, is a characteristic
of a powder rather than individual
particles and can be variable.
➢ The bulk density of a powder is
always less than the true density of
its component particles because the
powder contains interparticle voids.
➢ Thus, powder can possess a single
true density but can have many
different bulk densities, depending
on the way in which the particles are
packed and the bed porosity.

45
4. Bulkiness
Bulkiness(bulk) is specific bulk
volume, the reciprocal of bulk
density.
Formula for Bulkiness:
Bulkiness = 1/bulk density

Unit IV Micromeretics

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