MICROMERITICS

IN PHARMACY

BY :

G.LOKESH
K.KAVINESH KUMAR (Rep)
U.MADHIVANAN
. SARATHI
. KANCHANA
. ASMITA
.
 CONTENTS

• Introduction • Particle number

• Application in pharmacy • Methods for determining particle size

• Particle size and distribution • Particle shape

• Particle size distribution curve • Methods for determining surface

area.

• Number and weight distribution

• Derived properties
 INTRODUCTION

Micromeritics the science and technology

of small particles it also involves the study of
the fundamental and derived properties of the
individual as well as collection of particles.

U N I T:
Micrometer : µm
Micron : µ
which is equals to = 10^-6
APPLICATIONS IN PHARMACY

Absorption & Drug action

Release & Dissolution

Physical stability

Dose uniformity
PA RT I C L E S I Z E A N D PA RT I C L E S I Z E D I S T R I B U T I O N

A powder samples characterised by :

1. Particle shape
2. Particle size
3. Particle size distribution

If all the particles have the same diameter then the powder
sample is called a monodisperse system, but if all the particles are not of equal
size then that sample is called polydisperse system.
 PA RT I C L E S I Z E

The diameter of non spherical particles, measurement is

based on hypothetical sphere which is referred as equivalent spherical
diameter of particle. Thus it can be expressed in different ways;

1. Surface diameter(DS)

2. Volume diameter(DV)

3. Pojected diameter(Dp)

4. Stokes diameter(DST)

5. Feret’s diameter

6. Martin’s diameter
S U R FA C E D I A M E T E R ( D S )

The diameter of a sphere having the same surface area

ds =
as the particle and it is expressed as

where,
S = particle surface area

VO LU M E D I A M E T E R ( D V )

The diameter of a sphere having the same volume as

the particle and expressed by

dv =
Where,
V= particle volume
PROJECTED DIAMETER :
The diameter of a sphere having the
same observed area as the particle when viewed normal to
its most stable plain. It is expressed by microscopic
technique.

STOKE’S DIAMETER :
It is a diameter of an equivalent sphere
undergoes sedimentation at the same rate as the
asymmetric particle. This is measured by sedimentation
method.

FERET’S DIAMETER :
It is distance between two tangents on
opposite side of the particle parallel to some fixed direction.

M A RT I N ’ S D I A M E T E R :
Martin’s diameter is the length of a
line that bisects the particle image. The line can be drawn
in any direction but must be in the same direction for all
particles measured.
M E A N PA RT I C L E S I Z E :
Arithmetic mean of a powder is defined as the sum of the
particle sizes divided by the number of particles.
Different mean values are obtained based on length,
surface area or volume etc.

TYPES :

Length-number mean, dln

Volume surface mean

diameter, dvs
Volume weighted mean
diameter, dwm
Mean weight diameter, dvn

Surface-number mean
diameter, dsn
PA RT I C L E S I Z E D I S T R I B U T I O N

Particle size distribution is expressed as the number or weight of the

particles lying within a certain size range.

Particle size distribution is an important quality control tool in order to

obtain powders with a reproducible physical chemical and pharmacological
properties.
PA RT I C L E S I Z E D I S T R I B U T I O N C U RV E S

A particle size distribution (PSD) curve is a graphical

representation that shows the distribution of particle sizes within a given
sample. It is used to characterize the size range and frequency of particles in a
material.

Distribution curves are normally represented in the following

ways :

1.Frequency distribution curve

2.Log normal distribution curve
3.Cumulative frequency distribution
curve
4.Log-probability plot
1 . F R E Q U E N C Y D I S T R I B U T I O N C U RV E :
In this type, number or weight of particles lying within a
particular size range is plotted against the mean particle. Normal distribution
curve is symmetrical (bell shaped) around the mean.

The distribution of particles in a powder is termed

as unsymmetric or skewed, i.e., uneven around the mean. It normally shows
a long tail of larger particle size.
2 . L O G - N O R M A L D I S T R I B U T I O N C U RV E :
In this type, frequency on Y axis is plotted against log
mean particle size on X axis. Advantages of this curve is that the distribution
pattern is made symmetrical when compared to normal distribution curve.
Powder subdivide by crystallisation and milling methods exhibit log-normal
distribution.
3 . C U M U L AT I V E F R E Q U E N C Y D I S T R I B U T I O N C U RV E :
In this plot cumulative percentage oversize (or undersized)
is drawn against particle size.
If summation of frequencies is carried out from the
bottom upward the result is expressed as the percentage particles over size.
summation downwards gives percentage under size. Data yield a sigmoid
curve with the mode.
4 . LO G - P R OB A B I L I T Y P LO T :

A plot is drawn by taking log particle size on X axis and

cumulative percent frequency of the probability scale on Y axis. In this plot the
cumulative curve is converted into straight line having a point and slope.
NUMBER AND WEIGHT DISTRIBUTION :

It is possible to convert from normal distribution to

weight distribution if its log-normal, by using HATCH-CHOATE equation.
In microscopy, size distribution data is presented
in terms of number frequency while weight distribution is obtained by
sedimentation or sieve methods.
PA RT I C L E N U M B E R

It is defined as Number of particles per unit weight. If the

particles are spherical then the volume of particle is and mass will be (dvρ)/6 g
per particle. The number of particles per gram can be obtained as :

Where,
dvn = mean diameter based on volume and number
ρ = density of particle
M E T H O D S F O R D E T E R M I N I N G PA RT I C L E S I Z E

Various methods to estimate particle sizes are :

1. Optical Microscopy
2. Sieving Method
3. Sedimentation Method
4. Conductivity Method

Selection of a method largely largely depend on its intented

applications,desired type of diameter and type of distribution required. Data
obtained by one method may not match with data provided by other method
OPTICAL MICROSCOPY :

Range of particle size can be measured : 0.2-100 µm

The size is expressed as : dp (projected diameter), which describes

the diameter of sphere having the same area as the asymmetric particle when
observed under microscope.

This method directly gives number distribution ,which can be further

converted to weight distribution.

The following diameters can also be measured :

i) Martin’s diameter
ii) Feret’s diameter
iii) Projected area diameter
A D VA N TA G E D I S A D VA N TA G E

• Microscopy allows the observer to • Diameter is obtained from only two

view the particle dimensions. i.e., length and breadth.
Depth is not measured

• Any contamination or agglomeration

in the powder can be detected • This method is slow and tedious.

• Easy and simple

• Large sample is required
 SIEVING METHOD :

Range of particle size can be measured : 50-

1500 µm.

The size is expressed as : dsieve , which describes

the diameter of a sphere that passes through the sieve
aperture as the asymmetric particle.

This method directly gives weight distribution. The

method involves standard sieves and a mechanical sieve
shaker apparatus.
 METHOD :
 A sample (50 g) of powder is placed on top of
sieve. This sieves set this fixed to the
mechanical shaker apparatus and shaken for a
certain period of time.

 The powder retained on each sieve is weighed.

Frequently, the powder is assigned the mesh
number of the screen through which it passes
are on which it is retained.

 It is expressed in terms of arithmetic or

geometric mean of the two sieves.

 Data are analyzed for normal, log-normal,

cumulative percent, frequency distribution and
probability curves.
A D VA N TA G E D I S A D VA N TA G E

• It is inexpensive and simple method. • Lower limit of the particle size is

50µm.

• This method is rapid with

reproducible results. • There is chance of clogging of sieves
if the powder is not dried properly.

• Large sample size can be used.

• During shaking, attrition occurs
causing size reduction of particles.
This leads to error in estimation
S E D I M E N TAT I O N M E T H O D :

Range of particle size can be measured: 1-200 µm.

The size is expressed as : Stoke’s diameter dst , which describes

the diameter of an equivalent sphere having the same rate of sedimentation as
that of the asymmetric particle.

Application :
a) formulation and evaluation of suspensions
b) formulation and evaluation of emulsions
c) determination of molecular weight of polymers
 PRINCIPLE : This method is based on the principle of Stoke’s law, which
can be rearranged to get the Stoke’s diameter dst , of particles

dst =

h = distance of fall in time, t

= viscosity of the medium
= density of the particles
= density of the dispersion medium
g = acceleration due to gravity
METHOD :

The apparatus used for this method is called Andreasen

apparatus.

It consists of 550ml vessel containing 10ml pipette

placed in cylinder. It’s lower tip is 20cm below the
surface of suspension.

At different time intervals, 10ml samples are withdrawn

using two way stopcock and collected in a watch-glass.
Samples are evaporated and weighed.

The weight or the amount of particles obtained in each

time interval is referred to as weight under size. The
weights are converted into cumulative weight undersize.
The four curves are plotted and diameters are calculated
ADVANTAGE DISADVANTAGE

• The apparatus is inexpensive and • The method is laborious since

the technique is simple. separate analysis is required for
each poit on distribution curve.

• The results obtained are precise • Very small particles cannot be

provided the technique is determined
standardized.
CONDUCTIVITY METHOD :

Range of particle size can be measured: 0.5-500 µm.

The size is expressed as : volume diameter dv ,which

Describe the diameter of the sphere having the same volume as that of the
asymmetric particle.

Application :
a) Particle growth in suspensions and a solutions.
b) Distribution of drugs in a desired medium.
c) Effect of antibacterial agents on the growth of
microorganisms.
 Method:
The apparatus used for this method is called coulter counter.

This instrument operates on the principle that when a particle is

suspended in conducting liquid passes through a small orifice on
side of electrode, a change in electric resistance occurs.

This change in electrical resistance is termed as voltage pulse,

Which is related to particle volume.

Conductivity method is also known as stream scanning, i.e., a

fluid suspension of particles passes through a sensing zone in
which individual particles are electronically sized counted and
tableted

By changing the threshold settings gradually, number of

particles of each size range is obtained .thus the particle size
distribution curve can be obtained.
ADVANTAGE DISADVANTAGE

• Using coulter counter apparatus, • Coulter-counter method may be

approximately 4000 particles per unsuitable for polar and highly water
second can be counted. soluble materials due to solvation.

• Therefore size distribution complex • In, such case if a nonsolvent is used

can be completed in a relatively do suspend the particles, it may not
short period of time. produce adequate conductance.

• It gives reasonably accurate results. • Expensive instrument

PA RT I C L E S H A P E :

Particle shape will influence the surface area, flow of particles,

packing and compaction properties of particles. Sphere has minimum surface
area per unit volume.

It is possible to determine whether the particle is spherical or

asymmetric. In order to decide the shape the following expressions can be
used :
PROPERTY SPHERE ASYMMETRIC
PARTICLE

SURFACE AREA x

VOLUME x
S P E C I F I C S U R FA C E :

The specific surface of powder is defined as the surface area per unit
volume (Sv) or per unit weight (Sw).

Specific surface area per unit volume is expressed as :

=
where,
n is the number of particles.
The surface area per unit weight is shown as :

=
=

Where, is the true density of the particles.

When particles are spherical, then the equation is written as :

Where, = 6.0 for a sphere.

M E T H O D S F O R D E T E R M I N I N G S U R FA C E A R E A :

The surface area of a powder can be calculated using particle size data which
are obtained by one of the methods mentioned earlier.

The commonly used methods to determine the powder surface area are :

a) Adsorption method
b) Air permeability method
ADSORPTION METHOD :

• Surface area is most commonly determined based on Brunauer-Emmett-

Teller(BET) theory of adsorption.

• Most substances adsorb a monomolecular layer of gas under certain

conditions of partial pressure of gas under temperature.

• The adsorption process is carried out at liquid nitrogen temperature-196°C.

• One’s surface absorption has reached equilibrium the sample is heated at

room temperature and nitrogen gases desorbed. It’s volume is measured.

• As each molecule occupies fixed area, one can compute surface area of pre-
weighed sample.
 AIR PERMEABILITY METHOD :

• Powder is packed in sample folder.

• Packing appears as series of capillaries.

• Air is allowed to pass through the capillaries at

constant pressure.

• Resistance is created as air process through

capillaries thus causing pressure drop.

• Greater the surface area greater the

resistance.

• Air permeability is inversely proportional to the

surface area.
• The Kozeny-carman equation is used to estimate the surface area by this
method

Where,
A = cross sectional area of the bed,
ΔP= pressure difference of the plug
t = time of flow, seconds
l = length of the sample holder,
ε = porosity of the powder
sw= surface area per gram of the powder,
ŋ = viscosity of the air, (poise)
K = a constant ( 5.0 0.5) that accounts the irregular capillaries
V = volume of air flowing through the bed,
D E R I V E D P R O P E RT I E S O F P O W D E R S :

The properties of powder that are derived from the fundamental properties
(size,shape,surface area,etc..), are called derived properties of powder.

Some of the derived properties of powders are volume, density, porosity, etc..

A few application of them are given below :

Porosity : influences the dissolution of the drug.

Bulk density : helps in selecting containers for packing a dosage form.
Flow properties : helps in maintaining a uniform weight of tablets or capsules
-
during
production.
 DENSITY :

TRUE DENSITY :
It is the density of the material itself. It
is defined as :

True density =

Apart from true density, powder is

also characterised by granule density and bulk density.
T R U E D E N S I T Y D E T E R M I N AT I O N :

• True density can be determined by the following methods :

a) Helium displacement method ( for porous

powders)
b) Liquid displacement method ( for non-porous
powders)
 HELIUM DISPL ACEMENT METHOD (POROUS
POWDERS) :
Helium gas is selected as it does not adsorb on solid sample.

It enters the spores.

Very useful for estimation the true density of porous solids.

The instrument used in this method is called Helium pycnometer.

Air in the sample holder removed by vaccum.

Helium gas introduced through valve.

Pressure adjusted and set at particular valve with the help of

piston.
• At this position, the reading on the scale detonates U1.

• Place standard known true volume Vstd of stainless steel spheres.

• Air removed and helium gas introduced through valve and pressure adjusted.

• At this position the reading the reading on the scale denotes U2.

• The difference between U1 and U2 Gives the volume occupied by the standard.

• The last step involves determination of volume of sample. The standard is

replaced with sample and the reading is noted, US.
• The operating equation for the instrument is :

Vtest =

VStd = true volume of std sample

Vtest = true volume of the test sample
U1-U2 = volume occupied by the std sample
U1-US = volume occupied by the test sample
LIQUID DISPL ACEMENT METHOD (FOR NON-POROUS POWDER) :

• If the powder is non porous this method is used

• Weight of pycnometer = w1
• Weight of pycnometer + sample = w2
• Weight of sample, w3 = w2 – w1
• Weight of pycnometer + sample + solvent = w4
• weight of liquid displaced by sample = w4 – w2

true density =
Granule density :

• Granule density is determined for the granules that are employed in the
manufacture of tablets.

• Granule density is defined as :

Granule density =

• The volume of granules can be measured by mercury displacement method.

This method is same as that reported in the liquid-displacement method.
BULK DENSITY :

• It is mathematically defined as :

Bulk density () =

• Light powders have low bulk density

• Heavy powders have high bulk density

• The bulk density depends on particle size distribution and cohesiveness of

particles.
 METOD :

A weighed amount is introduced in a 100ml graduated

cylinder.

The cylinder is fixed on a bulk density apparatus. The

timer knob is set to 100 tapings.

For, reproducible results, the process of tapping is

continued until concurrent volume is achieved.

This final volume is the bulk volume. Then bulk density

is calculated using the equation.
POROSITY :

• The term porosity is used to define the number of small spaces or voids
present within a solid material.

• It is measure of void spaces in a material and is a fraction of the volume of

voids over the total volume, between 0 and 1 or as a percentage between 0-
100%.

porosity (

porosity (= (or) porosity (=

 PA C K I N G A R R A N G E M E N T S :

The arrangement of particles in a powder influences the

volume occupied by it. As, a result bulk density and porosity
are affected.

Types of packing between these ideal situations is possible :

a)porosities of powder(spherical particle) are about 26% it

means closed packing.
b)porosities of powder(spherical particle) are about 48% it
means loose packing.
c)porosities of powder, in general are between 30% and 50%
d)below 30% when particles differ greatly in size distribution
e) above 50% when particles are aggregated and flocculated
F L O W P R O P E RT I E S :

• Irregular flow of powder from the hopper produces tablet with nonuniform
weights.

• As a result content uniformity and dose precision cannot be achieved in the

production of tablets and capsules.

• Flow properties depend on particle size, shape, porosity and density of the
bulk powder.
PA RT I C L E S I Z E :

If the particle size is small (10µm), the powder flow restricted owing to van- der
waals, electrostatic and surface tension forces.

As the particle size increases, the flow property of powder increases, i.e., free
flowing.

An appropriate blend of coarse and fine particles improves the flow properties

N AT U R E O F PA RT I C L E :

Smooth surface Of particles improve the flow. Particles having high density
and low internal porosity tend to possess good flow properties.
MOISTURE CONTENT :

• The higher the higher the moisture content, the greater the risk of cohesion
and adhesion.

• Flow property can be improved by following method :

a) choosing optimum size of the granules, maybe around

400 to 800µm.

b) incorporating optimum amount of fines, about 15% w/w.

c) incorporating optimum concentration of lubricants such

as magnesium stearate, talc etc.
 ANGLE OF REPOSE :

The flow characteristics are measured by angle of

repose.

Angle of repose is defined as the maximum angle

possible between the surface of a pile of the
powder and the horizontal plane.

tanθ =

θ=
END