IPPP-II (Micro)

MICROMERITICS
Dereje K (PhD)
Pharmaceutics course team
School of Pharmacy, Jimma University,
Jimma, Ethiopia
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Objectives
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Objectives…
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Contents
Particle size and size distribution
Methods for determination of particle size and size distribution
Particle shape and surface area
Methods for determination of surface area
Derived properties of powders
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Introduction
 What is Micromeritics?
The science and technology of small particles
 Importance of micromeritics in the field of pharmacy

Particle size influences a large number of parameters in research,
development, and manufacturing of dosage forms.
The particle size range and distribution of particles in a given

product can influence its efficacy, stability, and safety
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Introduction….
The dimensions of particulate solids are important in achieving optimum
production of efficacious medicines.
The particle size of influences the subsequent physical performance of

the medicine and the pharmacological performance of the drug.
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Introduction….
 Particle size and size distribution influences:

the production of dosage forms.
 tablets
 capsule
 suspension
 emulsion
in a given product can influence its efficacy, stability, and safety.
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Introduction….
 Molecular dispersion – (size < 1 µm)
 Colloidal dispersion – (size 0.5 – 1µ m)
 Coarse dispersion – (size > 1 µm):
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Particle-size
Particle shape plays an important role in particle size determination.
 The simplest definition of particle size diameters is based on the

assumption that particles are spherical.
In reality, however, particles possess different shapes, for example,

rod, cubical, granular, etc
For this reason a solid particle is often considered to approximate to a

sphere which can then be characterized by determining its diameter
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Particle-size…
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Particle-size…
Because measurement is then based on a hypothetical sphere, which

represents only an approximation to the true shape of the particle, the
dimension is referred to as the equivalent diameter of the particle.
Equivalent diameter relate of the size particle to the diameter of a

sphere having the same surface area, volume, or rate of
sedimentation.
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Particle-size…
 Surface diameter, ds, is the diameter of a sphere having the same

surface area as the particle in question.
 Volume diameter, dv, is the diameter of a sphere having the same

volume as the particle in question.
 Projected diameter, dp, is the diameter of a sphere having the same

observed area as the particle when viewed normal to its most stable
plane.
 Stoks’ diameter, dst , a diameter of a sphere which describes an

equivalent sphere undergoing sedimentation at the same rate as the
asymmentric particle.
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Particle-size …..
 The projected area diameter is based on a circle of equivalent area to

that of the projected image of a solid particle.
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Particle-size…
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Particle Size Distribution
Any collection of particles is usually polydisperse.
It is therefore necessary to not only know the size of certain particles

but also to know how many particles of the same size exist in a
sample.
This is the particle-size distribution, and from it we can calculate an

average particle size for the sample
Thus, we need an estimate of the size range and the number or weight
fraction of each particle size.
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Particle Size Distribution
 Particle Size Distribution
 Refers to estimation of the size

range present and the number or
weight fraction of each particle size
range.
 Enables as to know the average

particle size
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Particle Size Distribution….
 nd 265.5
D mean = , = = 2.25𝜇𝑚
n 118
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Average Particle Size
 Edmundson derived a general equation for the average particle size,

whether it be an arithmetic, a geometric, or a harmonic mean diameter
1
  nd p f

p
d mean = ,   , where
  nd f

Where, n is the number of particles in a size range whose midpoint
d is one of the equivalent diameters
p is an index related to the size of an individual particle
(p = 1 , p = 2, or p = 3 is an expression of the particle length, surface, or
volume, respectively)
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Average Particle Size….
 The term p is an index related to the size of an individual particle

p = 1 (particle length)
p = 2 (particle surface)
p = 3 i(particle volume)
 The value of the index p also decides whether the mean is:
Arithmetic (p is positive),
Geometric (p is zero),
Harmonic (p is negative).
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 For a collection of particles, the frequency with which a particle in a

certain size range occurs is expressed by ndf .
 When the frequency index, f, has values of 0, 1, 2, or 3, then the

size frequency distribution is expressed in terms of the total
number (0)
Length (1)
Surface (2)
volume (3)
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Types of particle size distribution curves
Since most pharmaceutical substances contain a range of sizes, the

size distribution of the powder particles must also be determined to
characterize the powder and determine the particle size.
 Frequency Distribution curve

 When the number or weight of particles within a certain size range is
plotted against the size range or mean particle size,
a frequency distribution curve is obtained
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Particle Size Distribution…
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The normal distribution curve
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 The ideal resulting curve is a normal or Gaussian distribution.

 the distribution is symmetric around the mean, which is also the mode.
 Mode: what particle size occurs most frequently within the sample
 In a perfectly symmetrical distribution,

 the mean, median, and mode values are the same
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 Most pharmaceutical powders, however, as a consequence of milling,

tend to give skewed distributions
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 log-normal distribution
 Such distributions can be normalized by plotting frequency vs.

logarithm of particle size.
 Such a size distribution is referred to as a log-normal distribution.
 A log normal distribution has several properties of interest.
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a log-normal distribution
 Cumulative percent frequency over or under size distribution curve
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 Log probability distribution curve
 When a logarithm of particle size is plotted against the cumulative

percent frequency on a probability a linear relationship can be
observed (Log probability plots)
 Such a linear plot has the advantage of permitting characterization of

a log-normal distribution curve by means of two parameters:
the slope of the line
the geometric mean diameter (dg)
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 The reference point (geometric mean diameter (dg))
► is the logarithm of the particle size equivalent to 50% on the
probability scale, that is 50% size.
 The slope
►geometric standard deviation ( σg)
g = 50% size

16%oversize 84%undersize

16%numbersize 50% size 50% size
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Log probability plots
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Number and weight distribution
 Number distribution
collected by counting techniques such as microscopy
 Weight distribution
data based on a weight, rather than number distribution
achieved by sedimentation or sieving techniques
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 conversion number distribution to weight distribution can be obtained

by Hatch – choate equation
log dln = log dg + 1.151 log2 σg (Number Distribution)
log dln = Log d′g – 5.757 log2 σg (Weight Distribution)
dln = Length-number mean

dg = Geometric mean diameter for number distribution
d′g =Geometric mean diameter for weight distribution
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Example
 If the number distribution data gives dg = 7.1 m, and σ g = 1.43 or

log σg = 0.1553. using the hatch choate equation, calculate dln and
d′g
Log dln = log dg + 1.151 log2 σg
= 0.8513 + 1.151 (0.1553)2
= 0.8513 + 0.0278
= 0.8791 or dln = 7.57 µm
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 The geometric mean diameter for the weight distribution(d′g)
Log dln = log d′g – 5.757 log2 σg
0.8791 = log d′g – 5.757 (0.1553)2
Log d′g = 0.8791 + 0.1388
= 1.0179
d′g=10.4 µm
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Methods of particle size determination
Numerous methods
Should be carried out on a sample representative of the whole.
Methods of measuring the particle size

1. Microscopy
2. Sieve analysis
3. Sedimentation
4. Electronic determination of particle size
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Microscopy
 Particle size range:

Optical microscope 0.5 - 100 micrometer
Electronic microscope 0.01 - 1.0 micrometer
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Microscopy…
Procedures:
Preparing a slurry of several mg of powder in a liquid dispersion medium
in which the sample is insoluble.
One or two drops of the well mixed slurry is placed on a clean

microscope slide, and a cover slip is applied.
Several random fields are selected for counting.
The particle sizing may be accomplished by using:

Calibrated graticule
Calibrated micrometer
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Microscopy…
1. A calibrated graticule
Which is placed on the eye piece, and it consists of a series of

graded black and open circles.
The field is scanned from one side to the other using a mechanical
microscope stage and particles are sized according to the nearest
equivalent circle area.
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Microscopy…
2 A calibrated micrometer:
An emulsion or suspension is mounted on a slide and placed on a
mechanical stage.
The microscope eyepiece is fitted with micrometer by which the size of the
particle may be estimated.
Popular measurement are:
1. Martin diameter
2. Feret diameter
3. Projected area diameter
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Microscopy…
1. Martin diameter
2. Feret diameter
3. Projected area diameter
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Microscopy…
Diameter Definition
Feret The distance between tangents on opposite sides of the particle parallel
to some fixed direction that is Y direction
Martin The length of a line that bisects the particle image
Projected The diameter of a circle with the same area as that of particle observed
area perpendicular to the surface on which the particle rests
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Microscopy…
Advantages:
1. Low cost
2. It is simple and direct method.
3. Preparing the sample is simple.
4. Give information about the shape of particles.
5. Permanent record – photograph
6. The presence of agglomerate may be detected
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Microscopy…
Disadvantages:
Tedious
Time consuming
The diameter obtained is only from two dimension
To provide statistically sound data, a minimum of 300- 500

particles should be measured.
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Microscopy…
Alternative techniques to light microscopy

Scanning Electron Microscopy (SEM)
Transmission Electron Microscopy (TEM).
Both SEM and TEM analysis allow the lower particle-sizing limit to
be greatly extended over that possible with a light microscope.
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Scanning Electron Microscopy (SEM)
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Transmission Electron Microscopy (TEM)
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Example
 Determine the Average Particle Size of Powder Measured by an

Optical Microscope
∑𝑛 =330 ∑𝑛𝑑 =32300

𝑛𝑑 32300
𝑑𝑎𝑣 = = =98µm
𝑛 330
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Sieving
 This method uses a series of standard sieves calibrated by the
National Bureau of Standards.
 Sieves are made up of wire mesh with openings of known size.
 The term mesh is used to denote the number of openings per linear
inch.
 The method is generally used to measure coarser particles;

however, the method can be employed to measure particles as
small as 44 μm.
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Sieving…
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Sieving…
Procedure:
1. A nest of sieves with the coarsest on top is placed on the shaker
2. The powder sample of known weight is placed on the top of the

sieve.
3. The powder is shaken for a definite period of time
4. The powder is classified as having passed through one sieve and

being retained on the adjacent finer sieve.
5. The weight of the powder retained on each sieve is weighed
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Sieving…
 Particle diameter is considered as:
the size of the opening in the larger or finer sieve or
as the size of mean of the opening of the two sieves.
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Sieving…
Size Weight Distribution of a Powder for Particle Size Measurement by sieving
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Sieving…
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Sieving…
Advantages:
1. Very simple
2. Fast
3. Used in most of pharmaceutical preparations
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Sieving…
Disadvantages:
1. Production of electrostatic charges and so the particles may

aggregate together and not pass through the sieves.
2. Humidity present in the atmosphere causes the particles to stick

together.
3. The shape of the particles: ,e.g., particle present as needle shape, if

it is in vertical position it will pass but if it is in the horizontal position, it
will not pass.
4. The procedures should be standardized. ,
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Sedimentation
 The sedimentation method as based on the Stoke’s equation is

primarily used.
 The powder to be measured is suspended in a liquid in which material

is completely insoluble.
 The suspension is placed in a calibrated pipette from which the

samples are withdrawn from fixed depth at various times.
 The samples are evaporated to dryness and the residues are weighed.
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Stoke’s equation
ℎ
V 𝑉=
𝑡
Andreasen pipette
V = is the rate of settling,

d = is the diameter of the particles,
ρi = is the density of the particle,
ρe =is the density of the medium,
g =is the gravitational constant, and
η =is the viscosity of the medium
h =is the height of the liquid above the
sampling tube orifice
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Sedimentation…
Example (Ass)
A sample of powdered zinc oxide, density of 5.60 g/cm3, is allowed to

settle under the acceleration of gravity, 981cm/s2, at 250. The rate of
settling, ν is 7.30x10-3 cm/s; and density of the medium is 1.01g/cm3,
and its viscosity is 0.01gcm-1/s.
Calculate the stock‘s diameter of zinc oxide powder?
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Sedimentation…
The stoke’s equation holds exactly only for spheres falling freely
without hindrance and at a constant rate.
But applicable for irregular shape particles
Particles must not be aggregated or clumped together in suspension.

Requires deflocculating agent.
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Sedimentation…
For Stokes’ law to apply:

Flow of the particle is laminar or streamline
Must not be turbulance.
Falling at a constant rate
Whether the flow is turbulent or laminar is indicated by the

dimensionless Reynolds number (Re)
𝑣𝑑𝜌𝑒
𝑅𝑒 =
ղ
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Sedimentation…
 Stokes’s law cannot be used if Re is greater than 0.2 because

turbulence appears at this value
𝑅𝑒 ղ 𝑑 2 𝜌𝑖 − 𝜌𝑒 𝑔
𝑣= =
𝑑𝜌𝑒 18ղ
2
18𝑅 𝑒 ղ
𝑑3 =
(𝜌𝑖 − 𝜌𝑒 )𝜌𝑒 𝑔
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Sedimentation…
Example
If the material is suspended in a syrup containing 60% by weight of
sucrose, what will be the critical diameter, that is, the maximum diameter for
which Re does not exceed 0.2? The viscosity of the syrup is 0.567 poise,
and the density is 1.3 g/cm3.
2
18𝑅 𝑒 ղ
𝑑3 =
(𝜌𝑖 − 𝜌𝑒 )𝜌𝑒 𝑔
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Electronic determination of Particle size
Range of particle size determination: 0.5 - 500 microns.
Average diameter determined: volume diameter.
Method: The apparatus used is the Coulter Counter.
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Coulter Counter
Principle of operation
when a particle suspended in a conducting liquid passes through a

small orifice, on either side of which are electrodes, a change in
electric resistance occurs.
As the particle travels through the orifice, it displaces its own volume
of electrolyte, and this results in an increased resistance between the
two electrodes
The change in resistance, which is related to the particle volume,

cause a voltage pulse that is amplified and fed to a pulse heigh
analyser calibrated in terms of particle size
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Coulter Counter
Principle of Coulter counter.
This technique is based on calculable

alterations in electrical impedance
generated by nonconductive particles
suspended in an electrolyte.
A small opening (aperture) between

electrodes is the sensing zone via
which suspended particles pass.
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Coulter Counter
Advantages:
 This equipment can count large number of particles (500/min) very
rapidly.
 The apparatus yields highly reproducible results.
 Because of the large number of particles, statistics will be easy and

yield high level of confidence in the distribution of a sample.
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Coulter Counter
Disadvantages:
Cost of equipment is high
The possibility of orifice blockage by the particles specially in

heavy suspensions.
The electrolyte used must be specific and selective in which the

material to be counted is insoluble and is suitable in terms of
electrical resistance to the counted particles.
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Reading Assignment
Laser light scattering methods (Photon-correlation

spectroscopy)
Laser Diffraction
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Summary
Discuss the importance of knowledge of particle size and size
distribution.
List three types of distribution that might be used in expressing the

range of particle sizes contained in a given sample.
Discuss the different methods of particle size determination
After determining the particle size of 151 powder particles by the

microscopic method, the ∑ nd was reported to be 4,037.5. Determine
the average diameter of the powder particle.
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PARTICLE SHAPE AND SURFACE AREA
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Particle shape and surface area
 The shape affects the:

flow and packing properties of a powder
having some influence on the surface area.
 The surface area per unit weight or volume

is an important characteristic of surface adsorption and
dissolution rate studies
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Particle Shape
 A sphere has minimum surface area per unit volume.
 The more asymmetric a particle, the greater is the surface

area/volume
 Spherical particle is characterized completely by its diameter.
 As the particle becomes more asymmetric, it becomes increasingly

difficult to assign a meaningful diameter to the particle
the need for equivalent spherical diameters
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Particle Shape
 It is a simple matter to obtain the surface area or volume of a sphere

because for such a particle
𝑆𝑢𝑟𝑓𝑎𝑐𝑒 𝑎𝑟𝑒𝑎 = 𝜋𝑑 2
𝜋𝑑 3
𝑉𝑜𝑙𝑢𝑚𝑒 = where d is the diameter of the particle
6
 whose shape is not spherical, however, one must choose a diameter

that is characteristic of the particle and relate this to the surface area
or volume through a correction factor.
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Particle Shape
 Suppose the particles are viewed microscopically, and it is desired to

compute the surface area and volume from the projected diameter, dp,
of the particles
where αs is the surface area factor and ds is the equivalent surface diameter
where αv is the volume factor and dv is the equivalent volume diameter
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Particle Shape
 The surface area and volume “shape factors” are, in reality, the ratio
of one diameter to another.
 Thus, for a sphere
 The ratio αs/αv is used to characterize particle shape.
 When the particle is spherical, αs/αv = 6.0.
 The more asymmetric the particle, the more this ratio exceeds the
minimum value of 6.
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Specific Surface
 The specific surface is the surface area per unit volume, Sv, or per
unit weight, Sw,
 The surface area per unit weight is therefore
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Specific Surface…
 When the particles are spherical (or nearly so)
 because αs/αv = 6.0 for a sphere
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Specific Surface..
Example
What are the specific surfaces, Sw and Sv , of particles assumed to be

spherical in which ρ = 3.0 g/cm3 and dvs is 2.57 μm?
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Methods for determining surface area
 Two methods are commonly available that permit direct calculation of

surface area.
1. Adsorption Method
2. Air Permeability Method
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Adsorption Method
 the amount of a gas or liquid solute that is adsorbed onto the

sample of powder to form a monolayer
is a direct function of the surface area of the sample
 This process are demonstrated by the equation developed by

Brunauer, Emmett, and Teller, typically referred as the BET
method.
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Adsorption Method…
Where,
 V is volume of gas adsorbed at pressure P
 P is partial pressure of adsorbate
 Vm is volume of gas absorbed in monolayer
 P0 is saturation pressure of adsorbate at experimental temperature;
 b is a constant relating to the heats and condensation of the
adsorbate
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𝑝
 a plot of against p/p0 is used
𝑣(𝑝0 −𝑝)
to obtain a straight line
 the slope yield b
𝑣(𝑝0 −𝑝)
 Intercept yield Vm
𝑝
 The specific surface of the particles is
then obtained from
𝑝
𝑝0
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 M/σ is the molar volume of the

gas, 22,414 cm3/mole at
standard temperature and
pressure (STP)
 N is Avogadro’s number, 6.02 ×

Sw = 4.35m2/cm2 x Vmcm3/g 1023 molecules/mole
 Am is the area of a single close-

packed nitrogen molecule
adsorbed as a monolayer on the
M is the molecular weight, 28.01 g/mole, of surface of the particles
N2; σ is the density,
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 Example
 Using the Quantasorb apparatus, a plot of p/V(p0 − p) versus p/p0 was

obtained for a new antibiotic powder. The intercept = 0.00198 and the
slope is = 0.67942.
 Calculate Sw, the specific surface of the powder, in m2/g.
Vm= 1.46757 cm3/g Sw= 6.38 m2g
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Air Permeability Method
 The second method depends on the fact that the rate at which a
gas or liquid permeates a bed of powder is related
 The principal resistance to the flow of a fluid such as air through a

plug of compacted powder is the surface area of the powder.
 The greater is the surface area per gram of powder, Sw, the
greater is the resistance to flow.
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Air Permeability Method…
An air pump generates air pressure to a constant head by means of the pressure regulator
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Air Permeability Method…
 The Kozeny–Carman equation is the basis of most air permeability

methods.
 V = volume of air flowing through a capillary of internal diameter 'd' and length 'V' in 't'
seconds time, under pressure difference Δp
 A = Cross sectional area of the plug
 K = Constant (usually 5.0 ± 0.5) that takes account of the irregular capillaries.
 ε = is the porosity of the powder bed.
 Sw = Specific surface
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DERIVED PROPERTIES OF POWDERS
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94
Derived properties of powders
 Properties of powder
the two fundamental properties of any collection of particles
size distribution
 surface areas of powders
Derived properties
based on these fundamental properties
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Derived properties
Porosity
Flow property
Packing
Density
Compaction
Bulkiness
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Porosity
Fraction of powder bed that consists of free space

Bulk volume (Vb)
True volume ( Vp)
Void volume (V = Vb - Vp )
 Porosity refers to void spaces

Intraparticle spaces
Interspace or void porosity
Capillary space (cracks)
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Porosity
 The porosity or voids (ε) of the powder is defined as the ratio of the
void volume to the bulks volume of the packing.
ε = Vb – Vp = 1 − Vp
Vb Vb
Example : A sample of calcium oxide powder with a true density of 3.203 and
weighing 131.3g was found to have a bulk volume of 82.0cm3 when placed in a
100ml graduated cylinder. Calculate the porosity ?
Vp = 131.3g = 41.0cm3
3.203g/cm3
V = Vb – Vp, 82.0cm3 – 41.0cm3 = 41.0cm3
 ε = Vb – Vp  82 – 41 = 0.5 or 50%
Vb 82
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Packing Arrangements
Affected by porosity of particles/powders.
For uniformly sized spherical particles can have one of the following
packing arrangements
Closest/rhombohedral (ε = 26%)
Most open/loosest or cubic packing (ε = 48%)
(a) closest packing (b) loosest packet
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Packing Arrangements…..
 The particles in real powders are neither spherical nor uniform in

shape and size respectively.
 It is to be expected that any arrangements intermediate between

the two ideal packings, and most powders in practice have
porosities between 30 and 50%.
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Packing Arrangements….
 If the particles are of greatly different

sizes, however, the smaller may sift
between the larger to give porosities
below the theoretic minimum of 26%.
 Aggregation of particles leads to the

formation of bridges the porosity may
be above the theoretic maximum of
48%.
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Densities of Particles
True density
Granule density
Bulk density
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Densities of Particles…
True density (ρp)
 For non porous solids : by Liquid Displacement Method
 For porous solids : by the use of Helium densitometer
Granule Density (ρg)

 A method similar to liquid displacement method is used.
 Mercury is used since it fills the void spaces but fails to penetrate
into the internal pores of the particles.
Bulk Density (gb)
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Intraparticle porosity
Interspace or void porosity

 Is the relative volume of inter space voids to the bulk volume of the
powder, exclusive of the intra particle pores.
Total porosity
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ε Intra particle = Vg – Vp = 1 – Vp
Vg Vg
=1– Weight /true density

Weight/granule density
= 1 – Granule density
True density
𝜌𝑔
𝜀 =1−
𝜌𝑝
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ε inter space = Vb – Vg = 1 – Vg
Vb Vb
=1– Weight/granule density

Weight/bulk density
=1– Bulk density

Granule density
𝜌𝑏
ε inter space = 𝜀 = 1 −
𝜌𝑔
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ε total = Vb – Vp = 1 – Vp
Vb Vb
ε total = 1 – Weigh/true density
Weight/bulk density
𝜌𝑏
ε total = 1 −
𝑝
E.g The weight of sodium iodide tablet was 0.3439gm

and the bulk volume was measured by use of calipers
and found to be 0.0963cm3. The true density of NaI is
3.667 g/cm3. What is the bulk density and total porosity
of the tablet ?
Micromeritics
Bulkiness
Specific bulk volume or reciprocal of bulk density, is often called
bulkiness or bulk.
Bulkiness= 1/ρb
Important consideration in packaging of powders.
Bulkiness increase with a decrease in particle size.
Example: A selected powder has a true density of 3.5 g/cc. Experimentally, 2.5 g of
the powder measures 40 mL in a cylindrical graduate. Calculate the true volume,
void, porosity, apparent density, and bulkiness
Micromeritics
108
Flow Properties
Powders may be free flowing or cohesive (sticky)
The flowability of a powder is of critical importance in the production of

pharmaceutical dosage form.
Why is the flowability critical?
Micromeritics
109
Factors that affect the flow properties of powders
 Particle size
 Shape
 Porosity and Density
 Surface texture
 Moisture
Micromeritics
110
Methods to determine flow property
Hausner ratio
Carr’s index
Direct Method (Flow Rate)
Angle of Repose
Tap densitometer
Powder flow tester
Micromeritics
111
Methods to determine flow property
 Hausner Ratio = Tapped Density / Bulk Density

If the ratio is <1.25 the particles have good flow property
Carr’s Index = (Tapped density – Bulk density/Tapped density)*100

< 15 is excellent flow
Direct Method (Flow Rate)

There is an instrument called flow meter
which measures the weight of powders that flow per unit time.
Micromeritics
Methods to determine flow property..
Micromeritics
Methods to determine flow property…
 Angle of Repose
is the maximum angle possible between the surface of a pile of powder and the
horizontal plane
Tan  = h/r = µ,
< 25 Excellent
25 – 30 Good
Micromeritics
Methods to determine flow property…
Micromeritics
Improvement of powder flowability
Alteration of particle size and size distribution

Alteration of particle shape or texture
Formulation additives: flow activators
Alteration of process conditions
 Use of vibration-assisted hoppers
 Use of force feeders
Micromeritics 116
Compaction
 It is the property of powders to be compacted under certain pressure.
 The compression force affects a number of properties of the powders

such as ;
 Specific surface area
 Granule density
 Tablet disintegration time
 Porosity
 Tablet hardness
Micromeritics 117
Helium densitometer
 True density is normally measured by helium pycnometer, where the
volume occupied by the known mass of powder is determined by
measuring the volume of the gas displaced by the powder.
 The true density is an intrinsic property of a powder.
Micromeritics
118
Liquid Displacement Method
 It is the weight of the body divided by the volume of the liquid it

displaces. i.e the loss of weight of the body when suspended in a
suitable liquid.
Micromeritics
119
Bulk Density (gb)
 A sample of about 50cm3 of powder, which as previously been passed

through a U.S standard No. 20 sieve, is carefully introduced into a 100
ml graduated cylinder. The cylinder is dropped at 2 second intervals
on to a hard wood surface three times from a height of one inch. The
bulk density is then obtained by dividing the weight of the sample in
grams by the final volume in cm3 of the sample contained in the
cylinder.
Micromeritics
120
Summary
 Define Micromeritics, and explain its importance in pharmacy
 Fundamental properties of particles
 What are the equivalent diameter
 How to characterize the particle size distribution
 Methods of particle size measurement
 Methods of surface area measurement
 Discuss the derived properties of powder
Micromeritics

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MICROMERITICS

Particle size and size distribution

Methods for determination of particle size and size distribution

Particle shape and surface area

Methods for determination of surface area

Derived properties of powders

 Importance of micromeritics in the field of pharmacy

The particle size range and distribution of particles in a given

The particle size of influences the subsequent physical performance of

 Particle size and size distribution influences:

 Molecular dispersion – (size < 1 µm)

 Colloidal dispersion – (size 0.5 – 1µ m)

 Coarse dispersion – (size > 1 µm):

 The simplest definition of particle size diameters is based on the

In reality, however, particles possess different shapes, for example,

For this reason a solid particle is often considered to approximate to a

Because measurement is then based on a hypothetical sphere, which

Equivalent diameter relate of the size particle to the diameter of a

 Surface diameter, ds, is the diameter of a sphere having the same

 Volume diameter, dv, is the diameter of a sphere having the same

 Projected diameter, dp, is the diameter of a sphere having the same

 Stoks’ diameter, dst , a diameter of a sphere which describes an

 The projected area diameter is based on a circle of equivalent area to

Any collection of particles is usually polydisperse.

It is therefore necessary to not only know the size of certain particles

This is the particle-size distribution, and from it we can calculate an

 Particle Size Distribution

 Refers to estimation of the size

 Enables as to know the average

 Edmundson derived a general equation for the average particle size,

 The term p is an index related to the size of an individual particle

 For a collection of particles, the frequency with which a particle in a

 When the frequency index, f, has values of 0, 1, 2, or 3, then the

Since most pharmaceutical substances contain a range of sizes, the

 Frequency Distribution curve

The normal distribution curve

 The ideal resulting curve is a normal or Gaussian distribution.

 In a perfectly symmetrical distribution,

 Most pharmaceutical powders, however, as a consequence of milling,

 Such distributions can be normalized by plotting frequency vs.

 Such a size distribution is referred to as a log-normal distribution.

 A log normal distribution has several properties of interest.

 Cumulative percent frequency over or under size distribution curve

 Log probability distribution curve

 When a logarithm of particle size is plotted against the cumulative

 Such a linear plot has the advantage of permitting characterization of

 The reference point (geometric mean diameter (dg))

► is the logarithm of the particle size equivalent to 50% on the

probability scale, that is 50% size.

Number and weight distribution

 conversion number distribution to weight distribution can be obtained

log dln = log dg + 1.151 log2 σg (Number Distribution)

log dln = Log d′g – 5.757 log2 σg (Weight Distribution)

dln = Length-number mean

 If the number distribution data gives dg = 7.1 m, and σ g = 1.43 or

 The geometric mean diameter for the weight distribution(d′g)

Log dln = log d′g – 5.757 log2 σg

0.8791 = log d′g – 5.757 (0.1553)2

Log d′g = 0.8791 + 0.1388