Micromeritics

This presentation gives a concise view on the topic Micromeritics.

1. By
Dr. Sagar N Firke
Dept. of Pharmaceutics
Nanded Pharmacy College, Nanded
MICROMERITICS

2.  CONTENTS
Definition and Applications of Micromeritics
 Particle Characteristics
Ex., Size, Shape, Volume and Surface area
Powder Characteristics
Ex., Powder Size, Surface area, volume, Density and Flow Properties
 Particle Size Determinations
 Determination of Derived Properties
Ex., Bulk density, True Density, Carr’s Index etc

3. INTRODUCTION
 Definition: “It is science which involve the study of small Particles which are in few micron
size”.
 Applications
1. Release & Dissolution
2. Absorption & Drug Release
3. Physical Stability
4. Dose Uniformity

“Physical Stability of suspension depends upon surface area of the particles”
True or false

4.  PARTICLE CHARACTERISTICS
Each particle can be characterized and expressed by the following
properties
Ex, Size, Shape , Volume & Surface area.
 Particle Size
Particle size is expressed as the diameter which is related to an equivalent spherical diameter.
i. Surface Diameter, ds
ii. Volume Diameter, dv
iii. Projected Diameter, dp
iv. Stokes diameter, dst
v. Sieve Diameter, dseive

5. PARTICLE SHAPE
 Particle shape influence various properties such as surface area, flow property, packing
and compaction.
 Particles are highly irregular.
 It is possible to determine whether the shape is spherical or asymmetric.
Property Sphere Particle
Surface Area πd
s
2
αs x d
p
2

Volume (1/6) πd
s
3
αv x d
p
3

αs = πd
s
2
/ d
p
2
and αv = πd
s
3
/6 d
p
3

αs = π =3.124 and αv = π/6 = 0.524
Shape Factor = αs / αv =3.124/0.524 = 6
Minimum possible value for shape factor is 6, which represents a sphere.

6. Particle Shape

7. POWDER CHARACTERISTICS
 Powder is a collection of particle.
 Powders can be characterized and expressed by Ex, Powder size, Surface area, flow
property, particle number, volume and density.
 Powder size: There is no universal way to define size of a powder.
However powders can be expressed by Arithmetic mean and geometric mean.
 Arithmetic Mean:
Length number mean diameter = d
ln = ∑ nd/ ∑n
Where, n is the number of particles & d is the diameter

8. Volume surface mean diameter, d
vs


Volume surface mean diameter, d
vs


d
vs = ∑ nd
3
/ ∑nd
2

Ex: Following data were collected by means of an optical microscope, compute the arithmetic mean
particle diameter and mean volume surface diameter
Diameter (μm): 10 20 30
Number of particles (n): 03 02 01
Total Number of Particles= 6, sum of nd= 100
i. Arithmetic mean = = d
ln = ∑ nd/ ∑n = 100/6 =16.67 µm
ii. Mean Volume surface diameter = d
vs = ∑ nd
3
/ ∑nd
2

=Sum of nd
3
/ sum of nd
2

= 46000/2000 = 23.0 µm

9. Geometric Mean
 Geometric Mean:
The geometric mean diameter can be expressed
as
log d
geo =
∑ (n.logd)/ ∑n

Ex: Compute geometric mean particle diameter.
Size group (μm): 1-5 6-10 11-15 16-20
Number of particles (n): 18 60 40 06

Size
μm
Mean Size
μm (d)
No. of
Particles (n)
log d n.logd
1-5 03 18 0.4771 8.5878
6-10 08 60 0.9031 54.1860
11-15 13 40 1.1139 44.5560
16-20 18 07 1.2553 8.7871

∑n= 125 ∑ (nlog d) = 116.1169

dgeo= antiliog 0.9289 =8.49 μm

10. PARTICLE NUMBER
It is the number of particles per unit weight (N) is expressed in terms of volume-number mean
diameter, d
vn

Volume of as single particle =1/6 πd
3
vn
Mass of single particle = volume x density
= 1/6 πd
3
vn x ρ
There is following relationship

Weight of one particle Weight of the powder
--------------------------- = ---------------------------
1 number of Particle, N
1/6 πd
3
vn x ρ 1g
--------------- = ------- ie., N = 6/ πd
3
vn x ρ
1 N

11. Particle Size Determination Methods
Methods to estimate particle size are:
a. Optical Microscopy
b. Sieving Method
c. Sedimentation Method
d. Conductivity Method.
None of the methods are truly direct, because visual observation & measurement is not possible.

12.  Optical Microscopy
 Particle size in the range of 0.2 -100 μm
 Size is expressed as d
p
 This method directly gives number distribution
 The optical microscope has a limited resolving power of the lens.
 This method is used to determine
a. Particle Size analysis in suspension
b. Globule size distribution
c. Particle size analysis in aerosols

13. Components of Optical Microscope

14.  Procedure
• Eyepiece of the microscope is fitted with a micrometer.
• The eyepiece micrometer is calibrated with standard stage micrometer.
• In the calibration method First line of the eyepiece micrometer is coinside with first line
of the stage micrometer.
• Then find out the next line on the stage micrometer which is exactly coinciding with
eyepiece micrometer, count the number of divisions.
• The total length of stage micrometer is 1 mm consist of 100 divisions. Each division
length is 10 um.

15. Continue……..
If 40divisions of eyepiece micrometer is equal to 60 divisions of stage micrometer
1 Division of stage is 10 um
600/40 = 15 um
The calibration factor of eyepiece micrometer is found to be 15 um.
 Prepare the suspension of the powder sample using suitable solvent & transfer it on the
glass slide.
Around 625 particles must be counted in order to estimate the true mean.
The data obtained will be ploted on frequency distribution curve.

16. Sieving Method
 Particle having size range of 20 -1500 um are estimated by sieving method
 Size is expressed as d sieve.
Sieve No Aperture size µ Sieve No Aperture size µ
10 1700 44 325
12 1400 60 250
16 1000 85 35
22 710 100 36
25 600 120 34
30 500 150 36
36 425 170 35
Table: Sieve Number and Aperture size Fig: Sieve & Sieve Shaker

17. Method
 Standard Sieves of different mesh numbers are arranged in a nest with coarsest at the top.
 A sample (50 g) of the powder is placed on the top sieve.
 he sieves are fixed to the mechanical sieve shaker and shaken for certain period of time.
 The powder retained on the each sieve is weighed.
 Powder is assigned by mesh number of the screen through which it passes or on which it is
retained.
 It is expressed in terms of arithmetic mean or geometric mean of the two sieves.

18. Weight Size Distribution
Sieve No Arithmetic
mean size of
opening
Weight retained
on a sieve
g
% weight
retained
Cumulativ
e %
retained
30/45 470 57.3 13.0 13.0
45/60 300 181.0 41.2 54.2
60/80 213 110.0 25.0 79.2
80/100 163 49.7 11.3 90.5
100/140 127 20.0 4.5 95.0
140/200 90 22.0 5.0 100.0
Total Wt= 440 g
Wt on sieve
% Weight retained = ------------- X 100
Total wt of
powder
Table: Weight size distribution of a granular material measured by sieves

19. •Advantages
• It is Inexpensive, simple and rapid with reproducible results
•Disadvantages
• Lower limit of the particle is 50 um
•Only dry powder is required
•During shaking attrition occurs which causes size reduction.

20. Sedimentation Method ( Andreasen Pipette)
 Sedimentation Method may be used over a size range of 01 to 200 um.
Size is expressed as Stoke’s diameter, d
st


Where,
h= Distance of fall in time, t
no = Viscosity of the medium
Ps = Density of particles
Ps = Density of dispersion medium
g = Acceleration due to gravity

Fig: Andreasen Pipette Apparatus

21. Method
• Andreasen apparatus usually consist of 550 ml cylindrical vessel containing 10 ml pipette
sealed to a ground glass stopper.
•Prepare 2 % suspension of the powder in a suitable medium.
• Transfer the suspension in to apparatus.
• Place the stopper & shake the vessel.
• Around 10 ml samples are withdrawn using pipette and collect the sample in watch-glass.
• Samples are evaporated and weighed, the weight of particles obtained in each time interval
is reffered to as average diameter.

22. Conductivity Method
•Particle size ranging from 0.5 to 500 um is measured by conductivity method.
• This method gives number distribution
• Coulter counter is used to measure the particle volume.
• Size is expressed as volume diameter.
•This method is useful to study particle growth in suspension
• Approximately 4000 particles can be measured per second
• This method gives reasonably accurate results

23. Fig: Schematic diagram of Coulter Counter
 Conductivity Method is also known as
stream scanning
 Fluid suspensions of particle passes
through sensing zone.
 Individual particles are electronically
sized.

24. Method
 Particles are suspended in a electrolyte solution (NaCl), Suspension is filled in sample
Cell which has an orifice & maintains contact with external fluid.
 Electrodes are placed in solution( Inside the cell ) and in the suspension.
 A Constant voltage is applied across the two electrodes.
 When suspended particle passes through an orifice it displaces its own volume of
electrolyte into beaker.
 The net result is a change in electrical resistance, this change in electrical resistance is
termed as voltage pulse related to particle volume.

25. PARTICLE SIZE DISTRIBUTION CURVES
•When number or weight lying within a certain size range is plotted against the size range or
mean particle size is called frequency distribution curve.
•Distribution curve is important because it is possible that, two different sample may have
same average diameter but different distribution.
•Frequency curve tells us, what particle size occurs most frequently within the sample?
• There are different types of distribution curves
A. Normal frequency distribution curve
B. Log normal distribution curve
C. Cumulative frequency distribution curve

26. Normal Distribution Curve
The normal distribution curve
is symmetrical around the
mean.
 In this type of distribution the
positive & negative deviation
from the mean are uniform
 Normal distribution is not
common in pharmaceutical
powders
Fig: Frequency Normal distribution curve

27. Different Frequency Distribution Curves
Fig. Normal distribution curve Fig. Log normal distribution curve Fig. Cumulative frequency distribution curve

28.  In normal distribution curve the distribution is symmetric around the mean.

Size
Range
Mean
size
range d
Number of
particles
in each
size
%
Frequency
number of
particles
% Frequency
weight
distribution
1-5 03 18 06 0.03
6-10 08 60 20 1.75
11-15 13 105 35 13.17
16-20 18 56 19 18.64
21-25 23 40 13 27.78
26-30 28 11 04 13.79
31-35 33 06 02 12.31
36-40 38 04 01 12.53
Sum of the particles (n) = 300

29. Derived Properties ( Angle of Repose)
Def: “It is defined as maximum angle possible between surface of the pile of the powder and
horizontal plane”
 When weighed quantity of sample is transferred into the funnel it forms the pile at horizontal
plane.
The height of the pile (h) and the radius of the base (r) are measured with the ruler.
The angle of repose can be calculated by following formula.
Tan θ = h/r
θ= tan
-1
h/r
Where, h = Height of the pile
R = Radius of the pile

30.  Influence of lubricant/Glidants on angle of repose
 Glidants : Are the substances which reduces interparticle friction by
forming a layer around the particles and makes the surfaces smoother.
Examples: Colloidal Silica, Talc, Magnesium stearate, stearic acid etc.

Flow Properties Angle of Repose (θ)
Excellent < 25
Good 25-30
Passable 30-40
Poor/ very Poor >40

31. Bulk density, True density and Porosity
Bulk volume includes the true volume, volume of interparticle spaces (voids) and
intraparticle pores.
When particles are packed, it is possible that a large amount of gaps may be present
between the particles.
True volume is the volume exlusive of voids and
intraparticle spaces.

Mass of a sample
Bulk density = ------------------------- g/cc
Volume of a sample

32. Procedure
•Pass a quantity of powder through a sieve with apertures greater than or equal to 1.0
mm, if necessary.
•Into a dry graduated cylinder of 250 mL (readable to 2 mL), gently introduce, without
compacting, approximately 100 g of the test sample.
•Carefully level the powder without compacting, if necessary, and read the unsettled
apparent volume (V0 )
True Density
•The most common method used in the determination of true density is displacement
method. In this method usually organic liquids are used to determine true volume of a
powder sample.

33. •In this method true volume of granules is determined by measuring the volume
of Benzene displaced by the granules.
•The volume of Benzen displaced is equal true volume of the granules.
• The volume of gravity bottle is determined in terms of capacity of bottle.
•Fill the gravity bottle with Benzene and note the weight of bottle
•Transfer accurately weighed (1 gm) of granules d to preciously weighed specific
gravity bottle; reweigh the bottle.
•Bottle containing granules is filled with Benzene to the brim, followed by
weighing.
•The true volume and true density of granules can be calculated as per the given
formula.

34. (W3-W1) --- (W5-W4)
Volume of Benzene displaced = ------------------------------ ml
Density of Benzene
Capacity of Bottle = W2 – W1/ Density of Water
Where,
W1= Weight of empty gravity bottle
W2= Weight of gravity bottle + Water
W3= Weight of gravity bottle + Benzene
W4= Wight of gravity bottle + Granule sample
W5= Weight of gravity bottle+ granules + Benzene.

35. Mass of granules
True density of the microsphere = -------------------------------- g/cc
True volume of granules
Porosity or voids of the powder is
Void volume
Porosity = ---------------------
Bulk Volume
Bulk Volume – True Volume
Porosity = ---------------------------------
Bulk Volume

36. Applications of Bulk Density

 Bulk density is used to check the uniformity of bulk chemicals ( Quality Control)
 The selection of capsule size. Higher the bulk volume, lower will be the bulk
density and bigger the size of a capsule.
 Porosity influences the rate of disintegration & dissolution.

37. Carr’s Consolidation Index ( Compressibility)
Tapped density – Fluff density
Carr’s index = ------------------------------------ X 100
Tapped Density



Consolidation Index (%) Flow
5-15 Excellent
12-16 Good
18-21 Fair to passable
23-35 Poor
33-38 Very poor
> 40 Very very poor

38. References
1.Martins Physical Pharmacy and pharmaceutical sciences, sixth edition, pg no
442-468.
2. Textbook of Physical Pharmaceutics by CVS Subrahmanyam, Second edition,
Page No180-234.