Micromeritics

Amit M. Gupta
Lecturer
Agnihotri Collage of pharmacy, Wardha
What is Micromeritics?
The Science and Technology of small
particles is known as Micromeritics.

Micromeritics deals with-

• Particle size and Size Distribution
• Methods of Determining particles size
• Particle shape and surface area
• Pore size
 Importance of Study of Micromeritics
Knowledge and control of the size and the size range of
particle is of profound importance in pharmacy.

Size and surface area can be related to the physical,

chemical and pharmacological properties of a drug.

1.Particle size affect its release from dosage forms that are
administered orally, parenterally, rectally and topically

2. Physical stability and pharmacologic response of

suspensions, emulsion and tablets depends on particle
size.
3. It is also important in flow properties and proper mixing
of granules and. powders in tableting.

4. Both Tablets and capsules are produced using equipment

which controls the mass of drug and other particles by
volumetric filling. Therefore any interference with the
uniformity of fill volumes may alter the mass of drug
incorporated into the tablet or capsules. Thus reduce the
uniformity of the medicine.

5. Powders with different particle sizes have different flow

and packing properties which alter the volumes of
powder during each encapsulation or tablet compression.
6.The rate of solution depends on the
several factors. One factor is the particle
size. Thus particles having small
dimensions will tend to increase the rate
of solution.
 Different means of expressing particle size.
There are different means of expressing particle size:
Millimeter (mm)……. …10-3 meter
Micro meter (µ m) ……. ..10-6 meter
nano meter (nm)…….. 10-9 meter
pico meter …………….10-12 meter
fanto meter………………..10-15 meter

Particle Dimension in Pharmaceutical Disperse system

Particle size
Micrometer (µ m) Millimeter (mm) Disperse systems
0.5-10 0.0005 - 0.010 Suspension, fine emulsion
10-50 0.010- 0.050 Coarse emulsion, flocculated
suspension
50- 100 0.50- 0.100 Lower range of sieve range,
fine powder range
150-1000 0.150-1.000 Coarse powder range
1000- 3360 1.000- 3.360 Average granule size
Particle size and analysis
Stokes’ law/relation
1
2r ( d1 − d 2 ) g D ( d1 − d 2 ) g
2 2
 18vη  2
v= =
D =  
 ( d1 − d 2 ) g 
9η 18η

v: velocity of the sedimentation in cm/sec

r: particle radius in cm D: particle diameter in cm
d1: density of the particle in g/ml d2: density of the liquid in
g/ml
g = gravitational constant=980.7 cm·sec-2
Η = the viscosity of the medium in poises, i.e., g·cm-1·sec-1
(poise) in cgs units
Incidentally, the water at 20o has a viscosity of approximately
one centipoises (0.01 poise).
1 g·cm-1·sec-1 = 1 p = 100 cp =0.1Pa·s 1 cp =1 mPa·s
On micromeritics
Micromeritics is the science of small
particles; a particle is any unit of matter
having defined physical dimensions.

Micromeritics includes a number of

characteristics including particle size,
particle size distribution, particle shape,
angle of repose, porosity, true volume,
bulk volume, apparent density and
bulkiness.

A reduction in a powder’s particle size

increases the number of particles and
the powder’s total surface area.
 Particle size
Determined by microscopic method

size group of Middle value μm Number of “nd”

counted “d” particles per
particles/μm group “n”
40-60 50 15 750
60-80 70 25 1750
80-100 90 95 8550
100-120 110 140 15400
120-140 130 80 10400
∑n=355 ∑nd=36850

d av =
∑ nd 36850
= = 103.8
∑ n 355
 Particle size
Determined by sieving method
Sieve Arithmetic Weight retained % %Retained×
number mean opening (G) Retained Mean
(mm) opening
20/40 0.630 15.5 14.3 9.009
40/60 0.335 25.8 23.7 7.939
60/80 0.214 48.3 44.4 9.502
80/100 0.163 15.6 14.3 2.330
100/120 0.137 3.5 3.3 0.452
108.7 100.0 29.232

∑ ( %retained ) × ( ave size ) 29.232

d av = = = 0.2923 mm
100 100
Methods of determining particle size
 Optical Microscopy
 Sieving Methods
 Sedimentation Methods
Particle volume measurement:
 Coulter Counter Method (Electrical stream
sensing method)
 Laser light scattering methods.
Methods of determining surface area:
 Adsorption method
 Air permeability method
Microscopy
0.2 to 100 μm provide information of shape also
Principe of operation
•Optic or electronic measures
•Two dimensional projection
•Projection screen or
circles
•Image analysing programs
•Measures
•Feret diameters
•Equal circles
•Size range- 0.001-1000 µm
•Gives number average,or area
average
Benefits
– “Simple” and intuitive
– Give shape information
– Reasonable amount of sample

Drawbacks
– Statistic relevance “tedious” if
image analyse can not be used
– Risk for bias interpretation
– Difficult for high concentrations
– Sample preparation might be
difficult
 Sieving Method
Sieving method is an ordinary and simple method. It is widely
used as a method for the particle size analysis.
Range of analysis:
The International Standards organization (ISO) sets a lowest
sieve diameter of 45 µm and since powders are usually
defined as having a maximum diameter of 1000 µm, this
could be considered to be the upper limit.
In practice sieves can be obtained for size analysis over a range
from 5 to 125 000 µm.

ISO Range
Particle diameter (µm)

0.001 0.01 0.1 1 10 100 1000

Sample preparation and analysis condition
1. Sieve analysis is usually carried out using dry powders.

2. Although, for powders in liquid suspension or which

agglomerate during dry sieving, a process of wet sieving
can be used.
 Principle of Measurement:
Sieve analysis utilizes a woven, punched or
electroformed mesh often in brass, bronze or stainless
steel with known aperture (hole) diameters which form
a physical barrier to particles.

Most sieve analyses utilize a series, stack (

Load /Mountain or nest (layer) of sieves which have the
smallest mesh above a collector tray followed by meshes
which get progressively coarser towards the top of the
series.

A sieve stack usually comprises 6-8 sieves with a

progression based on a √2 or 2√2 change in diameter
between adjacent aperture.
Powder is loaded on to the coarsest sieve of the assembled
stack and the nest is subjected to mechanical vibration for,
say 20 minutes

After this time , the particles are considered to be retained

on the sieve mesh with an aperture corresponding to the
minimum or sieve diameter.

A sieving time of 20 minutes is arbitrary and BS 1796

recommends sieving to be continued until less than 0.2%
material passes a given sieve aperture in any 5 minutes
interval

Advantages: 1. This method is very simple.

2. Not expensive
3. Easy to operate

Disadvantages: 1. Not too much precise method.

2. Not applicable for all disperse systems.
 Sedimentation Methods
Sedimentation Method is also an ordinary and simple method
It is widely used as a method for the particle size analysis.
Range of analysis:

Centrifugal
sedimentation

Gravitational

0.001 0.01 0.1 1 10 100 1000

Particle diameter (µm)

Sample preparation and analysis conditions
In this method particle size can be determined by examining the
powder as it sediments out.
(a). In cases where the powder is not uniformly dispersed in a
fluid it can be introduced as a thin layer on the surface of the
liquid.

(b). If the powder is lyophobic, e.g. hydrophobic in water , it

may be necessary to add dispersing agent to aid wetting of
the powder.

(c). 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.

1. One of the type is based on measurement of particle in a retention

zone.
2. Another type uses a non-retention measurement zone.

An example of a non-retention zone measurement is known as the

pipette method.
In this method , known volumes of suspension are drawn off and the
concentration differences are measured with respect to time.
One of the most popular of the pipette methods was that developed by
Andreasen and Lundberg and commonly called the
Andreasen pipette.
The Andreasen fixed-position pipette consists of a 200 mm graduate
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.

The amount of powder can be determined by weight following drying

or centrifuging.

The weight of each sample residue is therefore called the weight of

undersize and the sum of the successive weight is known as the
cumulative weight of undersize. It can be expressed directly in
weight units or percent of the total weight of the final sediment..
The data of cumulative weight of undersize is used for the
determination of particle weight distribution, number distribution,
The largest particle diameter in each sample is then calculated from
Strokes’ Law.
The particle size may be obtained by gravity sedimentation as
expressed in Strokes’ law.
h dst2 (ρs- ρo) g
V= =
t 18ηo
18ηo h
or dst =√ (ρs- ρo) gt
Where ,
v = rate of settling
h = Distance of the fall in time , t
dst = the mean diameter of the particles based on the velocity of sedimentation
ρs= density of the particles
ρo = density of the dispersion medium
g = Acceleration due to gravity
ηo = Viscosity of the medium

Note: The question holds spheres falling freely without hindrance and at a
constant rate.
Coulter Counter Method (Electrical stream
sensing zone method)
Coulter Counter Method (Electrical stream sensing zone
method) is a sophisticated method. It is a precise and
accurate method.
Range of analysis:

Coulter counter

0.001 0.01 0.1 1 10 100 1000

Particle diameter (µm)

 Sample preparation and analysis conditions

1. Powder samples are dispersed in an electrolyte to

form a very dilute suspension.

2.The suspension is usually subjected to ultrasonic

agitation for a period to break up any particle

agglomerates.

3. A dispersant may also be added to aid particle

deagglomeration.
 Wallace Coulter ­ Coulter orifice ­ 1948­
1956
Cell
counter

vacuum

orifice

©J.Paul Robinson
 Principle of Measurement
1.The particle suspension is drawn through an aperture
accurately drilled through a sapphire crystal set into the wall
of a hollow glass tube.
2. Electrodes, situated on either side of the aperture and
surrounded by an electrolyte solution.
3. Monitor the change in electrical signal which occurs when a
particle momentarily occupies the orifice and displaces its
own volume of electrolyte..
4. The volume of suspension drawn through the orifice is
determined by the suction potential created by a mercury
thread rebalancing in a convoluted U tube.
5.The volume of electrolyte fluid which is displaced in the
orifice by the presence of a particle causes a change in
electrical resistance between the electrodes which is
proportional to the volume of the particle.
6.The change in resistance is converted between into a voltage
pulse which is amplified and processed electronically .

7. Pulses falling within pre-calibrated limits or thresholds are

used to split the particle size distribution into many different
size ranges.

In order to carry out size analysis over a wide diameter range it

will be necessary to change orifice diameter used, to prevent
Coarse particles blocking a small diameter orifice . Conversely,
finer particles in a large diameter orifice will cause too
small
a relative in volume to be accurately quantified.

Advantages: 1. It is one of the precise and accurate method.

2. Analysis range is wide.
Disadvantages:1. It is a sophisticated method.
2. It is a expensive method.
The first Coulter Counter
Other Methods to Determine
Particle Size
Laser Light Scattering

X-ray Sedimentation

Electrical Sensing Zone

Particle Size by Surface Area

Light energy diffraction or light scattering
Laser Holography
1.4 to 100 μm provide information on shape
Cascade impaction
Air is drawn through a
series of orifices of
decreasing size; the air flow
is normal to collecting
surfaces on which aerosols
are collected by inertial
impaction.

The particles, separated

stepwise by their
momentum differences into
a number of size ranges,
are collected simultaneously
PARTICLE PROPERTIES & FLOW:

 Particle size - Larger than 250µ are free flowing but as

size falls below 100µ it is cohesive; collection of powder
will be either-
A. Monodisperse ( having particles of same size ) or
B. Polydisperse (having particles of more than one
size).

 Particle shape - Spheres have minimum contact & hence

optimal flow; particle flakes have high surface to volume
ratio & poor flow

 Packing geometry–
 Characterization by porosity & bulk density
 Bulk density is always less than true density- due to
interparticle pores/voids
 Particle can have single true density but different bulk
densities
Derived properties of powders :
Apart from fundamental properties, there are
derived properties. These are based on
fundamental properties. These are :
1. Porosity,
2. Packing arrangements,
3. Densities of particles: Bulk density, Tap
density, Granule density. Dense particles are less
cohesive than less dense particles of the same
size & shape.
4. Particle volume: Bulk volume, Tap volume,
Void volume. Instrument used for measurement
is coulter counter. Dilute suspension is passed
through a small orifice and change in electric
resistance is measured.
coulter counter
5. Particle surface area: Surface area is
important characteristic for
understanding surface adsorption and
dissolution rate studies. Methods for
determining surface area:
A. Adsorption method,
B. Air permeability method
A. Adsorption method:
An instrument used to obtain data for calculation of surface area is Quantasorb .
the absorption and desorption is measured with thermal conductivity detector,
when a mixture of helium and nitrogen is passed through the cell, containing
powder. Here nitrogen is absorbate gas and helium is inert and is not adsorbed on
surface.
With the help of mathematical calculations and graph studies, nitrogen adsorbed
and area are calculated.

 Principe of operation  Range

– Measures the adsorption of – 0.01 to over 2000 m2/g.
gas molecules  Benefits
• Remove adsorbed – Well established
molecules
– High precision
• Introduce gas
• Measure pressure – Gives inner pores
differences  Drawbacks
– Over estimation of available area
– Experimental difficulties
Air permeability method
 B. Air permeability method:
Here the principle is “resistance to the flow of a fluid
through a plug of powder is the surface area of powder.
“Greater the surface area, the greater will be the
resistance to flow.”
The instrument used is Fisher subsieve sizer.

 Measures:  Benefits
– Specific area – Simple equipment
 Principe of operation – Relevant for many applications
 Drawbacks
– Measures the pressure drop in a
particle bed – Has to know
• Porosity
• Kozenys constant
– Needs uniform density of particles
– Conditions
• Laminar flow
• Know Kozenys constant
• Homogenous particle bed
 6. Bulkiness- Reciprocal of bulk density,
7. Flow properties: Powders may be free-flowing or
cohesive.
Factors those affect flow properties are
a) particle size, b) shape, c) porosity,
d) density, e) texture.
Flow rate is expressed by Pressibility Index (I)=[1-v/vo]100
8. Compaction
9. Angle of repose
10. Carr’s Index: (Tapped density - Poured density) x 100

Tapped density

11. Hausner’s ratio: Tapped density x 100

Poured density
Other characteristics of micromeritics
Vbulk − V 1
Void = bulkiness(B) =
Vbulk ρa

Porosity = Void ×100

Vbulk − V
Porosity = × 100
Vbulk

weight of the sample

apparent density(ρ a ) =
Vbulk

weight of the sample

true density(ρ t ) =
V
POWDER FLOW
Factors affecting packing geometry:
Particle size & size distribution- void spaces
in between can be filled with fine particles

Particle shape & texture-open structure vs.

tight packing

Surface properties-electrostatic forces

Handling & processing conditions-prior to

flow
FLOW through orifice
 Factors:
1. ORIFICE DIAMETER:
 Powder flows proportional to orifice diameter
provided that powder head remains considerably
greater than orifice diameter.
2. HOPPER WIDTH:
 Make adjustments so that minimum hopper widths
are large enough to produce arch stresses greater than
arch strength.
3. HEAD SIZE:
 Pressure changes with powder head size.
4. HOPPER WALL ANGLE:
 Powders with low wall friction angles will empty freely
5. MASS FLOW:
 First in first out
6. FUNNEL FLOW:
 “Rat hole”
CHARACTERIZATION OF POWDER
FLOW
 Indirect Methods:
2. Angle of repose
3. Shear cell determinations which gives
relationship between flow factors & powder
flowability
4. Bulk density measurements-%
compressibility & flow, Carr method
5. Critical orifice diameter-direct measure of
powder cohesion & arch strength
POWDER FLOW
 Direct Methods:
2. Hopper flow rate
3. Recording with flowmeter

HOW TO IMPROVE FLOW

• Alter particle size & size
distribution
• Alter particle shape or texture
• Alter surface forces
• Formulation additives
• Vibration assisted hoppers
• Force feeders
 Angle of repose
The angle of repose is a parameter used to estimate the
flowability of a powder.

h h
tangentθ = = µ θ
r r
Powders with low angles of repose will flow freely and
powders with high angles of repose will flow poorly.
A number of factors, including shape and size, determine the
flowability of powders.
Shape: Spherical particles flow better than needles.
Size: Very fine particles do not flow as freely as large
particles.
a) 250-2000 μm: flow freely if the shape is amenable
b) 75-250 μm: may flow freely or cause problems, depending
on shape and other factors
c) less than 100 μm: Flow is problem with most substances.
Bulk density

The particle density or true density of

a particulate solid or powder, is the
density of the particles that make
up the powder, in contrast to the
bulk density, which measures the
average density of a large volume
of the powder in a specific medium
(usually air).
Measurement OF Bulk density
 The measurement of particle density can be done in a
number of ways:

Archimedes' principle
 The powder is placed inside a pycnometer of known
volume, and weighed. The pycnometer is then filled with a
fluid of known density, in which the powder is not soluble.
The volume of the powder is determined by the difference
between the volume as shown by the pycnometer, and the
volume of liquid added (i.e. the volume of air displaced).
A similar method, which does not include pore volume, is
to suspend a known mass of particles in molten wax of
known density, allow any bubbles to escape, allow the wax
to solidify, and then measure the volume and mass of the
wax/particulate brick.

 A slurry of the powder in a liquid of known density can

also be used with a hydrometer to measure particle density
by buoyancy.
 Another method based on buoyancy is to measure the weight of the sample in
air, and also in a liquid of known density.

 A column of liquid with a density gradient can also be prepared: The column
should contain a liquid of continuously varying composition, so that the
maximum density (at the bottom) is higher than that of the solid, and the
minimum density is lower. If a small sample of powder is allowed to settle in
this column, it will come to rest at the point where the liquid density is equal
to the particle density.

Volumetric measurement
 A gas pycnometer can be used to measure the volume of a powder sample. A
sample of known mass is loaded into a chamber of known volume that is
connected by a closed valve to a gas reservoir, also of known volume, at a
higher pressure than the chamber. After the valve is opened, the final pressure
in the system allows the total gas volume to be determined by application of
Boyle's law.

 A mercury is an instrument that allows the total volume of a powder to be

determined, as well as the volume of pores of different sizes: A known mass
of powder is submerged in mercury. At ambient pressure, the mercury does
not invade the interparticle spaces or the pores of the sample. At increasing
pressure, the mercury invades smaller and smaller pores, with the relationship
between pore diameter and pressure being known. A continuous trace of
pressure versus volume can then be generated, which allows for a complete
characterization of the sample's porosity.
True density
The density of the particles that make
up a powder or particulate solid, in
contrast to bulk density, which
measures the average density of a large
volume of the powder in a specific
medium (usually air).
Carr index
 The Carr index is an indication of the compressibility of a powder. It is
calculated by the formula ,
VB - VT
C = 100 × --------------
VB
 where VB is the freely settled volume of a given mass of powder, and VT is
the tapped volume of the same mass of powder. It can also be expressed as
,
ρB
C = 100 × ( 1- ------------)
ρT
 where ρB is the freely settled bulk density of the powder, and ρT is the
tapped bulk density of the powder.

 The Carr index is frequently used in pharmaceutics as an indication of the

flowability of a powder. A Carr index greater than 25% is considered to be an
indication of poor flowability, and below 15%, of good flowability.

 The Carr index is related to the Hausner ratio, another indication of

flowability, by the formula
1
C = 100 × ( 1 - ------- )
H
 Both the Hausner ratio and the Carr index are sometimes criticized, despite
their relationships to flowability being established empirically, as not having
a strong theoretical basis. Use of these measures persists, however,
because the equipment required to perform the analysis is relatively cheap
and the technique is easy to learn.
 Hausner ratio
 The Hausner ratio is a number that is correlated to the of a
powder or granular material. It is calculated by the formula

ρT
H= --------------
ρB
 where ρB is the freely settled bulk density of the powder, and
ρT is the tapped bulk density of the powder. The Hausner ratio
is not an absolute property of a material; its value can vary
depending on the methodology used to determine it.

 The Hausner ratio is used in a wide variety of industries] as an

indication of the flowability of a powder. A Hausner ratio greater
than 1.25 is considered to be an indication of poor flowability.
The Hausner ratio (H) is related to the Carr index (C), another
indication of flowability, by the formula H = 100 / (100 − C). Both
the Hausner ratio and the Carr index are sometimes criticized,
despite their relationships to flowability being established
empirically, as not having a strong theoretical basis. Use of
these measures persists, however, because the equipment
required to perform the analysis is relatively cheap and the
technique is easy to learn
 Porosity is a measure of the void spaces in a
material, and is measured as a fraction, between
0–1, or as a percentage between 0–100%. The
term is used in multiple fields including
pharmaceutics, ceramics, metallurgy, materials,
manufacturing, earth sciences and construction.
 It is defined by the ratio:
Vv
φ= ---------
VT
where VV is the volume of void-space (such as
fluids) and VT is the total or bulk volume of
material, including the solid and void
components. Both the mathematical symbols φ
and n are used to denote porosity.