Micromeritics

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 Studying 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 dissolution 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 ( m) . ..10-6 meter

nano meter (nm).. 10-9 meter

pico meter .10-12 meter
famto meter..10-15 meter

Particle Dimension in Pharmaceutical Disperse

system
Particle size
Micrometer ( m) Millimeter (mm) Disperse systems
0.5-10
10-50

0.0005 - 0.010
0.010- 0.050

50- 100
150-1000
1000- 3360

0.50- 0.100
0.150-1.000
1.000- 3.360

Suspension, fine emulsion

Coarse emulsion,flocculated
suspension
fine powder range
Coarse powder range
Average granule size

Particle size and analysis

Stokes law/relation

2r d1 d 2 g D d1 d 2 g
v

9
18
2

18v

D
d1 d 2 g

v: velocity of the sedimentation

r: particle radius
D: particle diameter in cm
d1: density of the particle d2: density of the liquid
g = gravitational constant=980.7 cmsec -2

1
2

= the viscosity of the medium in poises, i.e.,

gcm-1sec-1 (poise) in cgs units
Incidentally, the water at 20 degree centigrade
has a viscosity of approximately one
centipoises (0.01 poise).
1 gcm-1sec-1 = 1 p = 100 cp

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 powders particle size increases the

number of particles and the powders total surface
area.

The size of a sphere is usually expressed in terms of

diameter. As the degree of asymmetry of particles
increases, it is difficult to express size in terms of a
meaningful diameter.
Equivalent spherical diameter is used in this cases where
the size of a particle is compared to the diameter of a
sphere having the same surface area, volume, weight or
rate of sedimentation.
Equivalent surface diameter (ds) is the diameter of a
sphere having the same surface area as the particle in
question.
Define equivalent volume diamtre (dv), equivalent weight
diameter (dw), equivalent stokes diameter (dst) in the
same way.

Methods of determining particle size

Optical Microscopy
Sieving Methods
Sedimentation
Particle volume measurement
Methods of determining surface area

Adsorption method
Air permeability method

Optical Microscopy
Ordinary microscope can be used to determine particle
size having a range of 0.2 to 100 m.

Procedure
An emulsion/suspension of the substance under
examination is prepared first.
The emulsion/suspension should be sufficiently
dilute.
The emulsion or suspension is then mounted on a
mechanical stage of the microscope.

 The

microscope eyepiece is fitted with a

micrometer by which the size of the particles
or droplets can be measured.
The field can be projected onto a screen where
the particles are measured more easily
A photograph can also be taken from which a
slide is prepared and projected on a screen for
measurement.

 Popular

measurements in microscopic
method are1.Martin diameter
2.Feret diameter

Martin Diameter
This

is not an diameter in its actual sense but

the common basis of a group of diameters.
The Martin diameter, xM, is that chord
dividing the projection area of the particle into
two equal halves.

 orientation

of measurement

 Martin

Diameter, Maximal (MARTIN_MAX), or

Minimal (MARTIN_MIN)
This is the maximal or minimal Martin diameter after
consideration of all possible orientations (0...180).
The Martin diameters for a sufficient number of
orientations are calculated, and their maximum or
minimum, respectively, is selected.
Martin Diameter, Mean Value (MARTIN_MEAN)
This is the mean value of the Martin diameters of all
possible orientations according to the principle
described above.

Feret Diameter
It is defined as the distance between two parallel tangents of
the particle at an arbitrary angle.
Feret Diameter, Maximum (FERET_MAX) or Minimum
(FERET_MIN)
Maximal or minimal Feret diameter after consideration of
all possible orientations (0...180). The Feret diameters for
a sufficient number of angles are calculated, and their
maximum or minimum is selected. If a particle has an
irregular shape, the Feret diameter usually varies much
more than with regularly shaped particles. The maximum
can therefore be significantly larger, the minimum
significantly smaller than the diameter of the equivalent
circle.

 Feret

Diameter, Mean Value

(FERET_MEAN)
Mean value of the Feret diameters over
all orientations according to the
principle described above.

Advantages of microscopic method

Simple

and intuitive
Give shape information
Reasonable amount of sample

Disadvantages of microscopic method

Diameter of particle is obtained only from two dimensions
of the particle :length and breadth. No estimation of depth
(thickness) of the particle is ordinarily available
The number of particles that must be counted (300-500) to
obtain a good estimation of the distribution makes the
method slow and tedious.
So, microscopic examination of a sample should be
undertaken even the when other methods of particle
analysis are being used, because the presence of
agglomerates and particles of more than one component
may often be detected.

Particle size
Determined by microscopic method
size group of
counted
particles/m

Middle value m
d

Number of
particles per
group n

nd

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

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 m and since powders
are usually defined as having a maximum diameter of
1000 m, this could be considered to be the upper
limit.

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 ) 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.

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 usually
performed.

ADVANTAGES AND DISADVANTAGES

OF SEIVING METHOD
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.

Particle size

Determined by sieving method

Sieve
number

Arithmetic
mean opening
(mm)

Weight retained
(G)

%
Retained

%Retained
Mean
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

d av

%retained ave size 29.232

0.2923 mm
100

100

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

10

Particle diameter (m)

100

1000

 Sedimentation

method is based on the principle of

stoke's law
The equation is applicable only for particles having
spherical shape, falling freely without hindrance and
at a constant rate.
The law can be applied to irregularly shaped
particles as long as one realizes that the diameter
obtained is a relative particle size equivalent to that
sphere falling at the same velocity as that of the
particles under consideration.

 The

particles must not be aggregated or

clumped together in the suspension because
such clumps would fall more rapidly than the
individual particles and erroneous result may
occur.
The proper deflocculating agent must be found
for each sample that will keep the particles free
and separate as they fall through the medium.

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 particle diameter in each sample is then

calculated from Stokes Law.
Note: The method is applicable for spheres falling freely
without hindrance and at a constant rate.

Coulter Counter Method

Coulter Counter Method is a sophisticated method. It is
a precise and accurate method.
The method is based on determination of particle size by
measuring particle volume.

Range of analysis:

0.001

0.01

Coulter counter

0.1

10

Particle diameter (m)

100

1000

Sample preparation
preparation and
and analysis
analysis conditions
conditions
Sample

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
The particle suspension is drawn through an aperture
accurately drilled through a sapphire crystal set into the
wall of a hollow glass tube.
Electrodes, situated on either side of the aperture and
surrounded by an electrolyte solution.
Monitor the change in electrical signal which occurs
when a particle momentarily occupies the orifice and
displaces its own volume of electrolyte.
The volume of suspension drawn through the orifice is
determined by the suction potential created by a mercury
thread.

 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.
The change in resistance is converted between into a
voltage pulse which is amplified and processed
electronically .

 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 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 m provide information on shape

PARTICLE PROPERTIES & FLOW

Particle size - Larger than 250 are free flowing
but as size falls below 100 it is cohesive;
collection of powder will be eitherA. Monodisperse ( having particles of same size )
or
B. Polydisperse (having particles of more than one
size).
Particle shape - Spheres have minimum
contact/surface area & hence optimal flow; particle
flakes have irregular shape & high surface to
volume ratio & poor flow.

Other properties of powders :

Apart from fundamental properties, there are some
other properties. These are based on fundamental
properties. These are :
1. Porosity
2. Packing arrangements
3. Densities of particles: Bulk density, Tapped
density. Dense particles are less cohesive than less
dense particles of the same size & shape.
4. Particle volume: Bulk volume, Tap volume.

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

Bulk density :The weight per volume of a powder. It is

defined as the mass of many particles of the material
divided by the total volume they occupy. The total
volume includes particle volume, inter-particle void
volume and internal pore volume.
Tapped density: Tapped density is the term used to
describe the bulk density of a powder (or granular solid)
after consolidation/compression prescribed in terms of
"tapping" the container of powder a measured number of
times, usually from a predetermined height. The method
of "tapping" is best described as "lifting and dropping".

Bulk

volume: The bulk volume of a

powder is the weight of the powder
divided by the density.
Tapped volume: The tapped volume of a
powder is the weight of the powder (after
tapping a certain period of time) divided
by the density.

Adsorption method for measurement of surface

area:
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.

Flow properties: Powders may be free-flowing or

cohesive. Factors those affect flow properties area) particle size b) shape c) porosity
d) density e) texture.

Compaction

Angle of repose

Carrs Index: (Tapped density - Poured density) x 100

Tapped density

Hausners ratio: Tapped density x 100

Poured density

Angle of repose (measurement of flow property)

The angle of repose is a parameter used to estimate the flowability of a powder.

tangent

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 m: flow freely if the shape is amenable
b) 75-250 m: may flow freely or cause problems, depending on shape
and other factors
c) less than 100 m: Flow is problem with most substances.

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 ,
B
C = 100

( 1- ------------)
t

where B is the freely settled bulk density of the powder,

and t 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

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
T
H= -------------B
where B is the freely settled bulk density of the powder,
and T 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.