MICROMERITICS

1
OUTLINE
Introduction

Particle Size and Distribution

Methods for Determining Particle Size

Particle Shape and Surface Area

Methods for Determining Surface Area

Pore Size
2
Derived Properties of Powder
 Introduction
 MICROMERITICS
 Science and technology of small particles

 Colloidal dispersions = too small to be

seen in the ordinary microscope
 Particles of a pharmaceutical emulsions
and suspensions and the fines of
powders = optical microscope
 Particles having the size of coarser
powders, tablet granulations, and the 3
granular salts = sieve range
 Introduction

 Units of particle size:

 micrometer or microns
 milli micron or nanometer

 Sizeand surface area of the drug is

significant to:
 Physical, chemical and pcol prop of drugs
 Release from dosage forms that are
administered orally, parenterally, 4

rectally, and topically

MICROMERITICS
(SCIENCE AND TECHNOLOGY OF SMALL
PARTICLES)

Categories of properties:
1. Fundamental Properties- inherent in all
individual particles
-defined individually
Ex. Particles size and shape, particle size
distribution, surface area

2. Derived properties
-dependent on the fundamental properties
Ex. Porosity, density , flow properties, packing
arrangement or bulkiness
 Particle Size and Distribution

 In
a collection of particles of more
than 1 size, 2 properties are
important:
 The shape and surface area of the
individual particles
 The size range and number or weight
of particles present

6
 Particle Size and Distribution

 Anycollection of particles is usually

polydisperse
 It is necessary to know not only the size of a
certain particle, but also how many
particles of the same size exist in the
sample
 estimate of the size range present and the
number of weight fraction of each particle
size
 This is particle size distribution and from it
we may calculate an average particle size
for the sample 7
Methods for Determining Particle
Size

Optical
Sieving
microscopy

Particle
Sedimentation Volume
Measurement 11
Optical microscopy

 Use of the ordinary microscope for

particle size measurement in the
range of 0.2 micron- 100micron

 PROCEDURE: an emulsion or
suspension, diluted or undiluted is
mounted on a slide and the
microscope eyepiece is fitted with a
micrometer by which the size of the
particles may be estimated 12
Optical microscopy

 The field can be projected onto a

screen where the particles are
measured easily or a photograph can
be taken from which a slide is
prepared and projected on a screen
for measurement

13
Optical microscopy

MARTIN • Length of the line that bisects the

Diameter particle image

FERET • Distance between two tangents on

opposite sides of the particle parallel to
Diameter some fixed direction

PROJECTED • Diameter of the circle with the same

area as that of the particle observed
AREA perpendicular to the surface on which
Diameter the particle rests 14
 1.Martin diameter
Optical microscopy 2.Feret’s diameter
3.Projected area
diameter

15
 Optical microscopy

 DISADVANTAGES
 The diameter is only two dimensions of
the particle
 No estimation of the depth (thickness)
 300 to 500 particles that must be
counted (slow and tedious)

16
 Sieving

 Uses a series of standard sieves

calibrated by the National Bureau of
Standards
 According to the method of the USP for
testing powder fineness:
 a definite mass of sample is placed on a
proper sieve in a mechanical shaker.
 The powder is shaken for a definite period
of time
 The material that passes through one sieve
and is retained on the next finer sieve is
collected and then weighed 17
Sieving

18
Sieving

19
 Sieving
V

 Mesh number
 Number of square openings per linear
inch
 mesh # =  mesh size

20
 Sieving

Example Data: 1. What % of

Mesh # Weight of
powder is smaller
Powder
than mesh 40?
2. What % of
20 10
powder is larger
40 15 than mesh 60?
60 20 3. What % of
powder is smaller
80 25 than mesh 60 and
Collecting 30
larger than mesh
Pan
80? 21

TOTAL 100g
 Sieving

 Sieving
errors can arise from a
number of variables (Disadvantages)
1. Sieve loading
2. Duration and intensity of agitation

22
Sedimentation

1. Stoke’s law (Gravity by Sedimentation):

OR

v = rate of settling
h = distance of fall
t = time of fall
dst = mean diameter based on
ρ0 = density of particles
g = acceleration due to gravity
23
η0 = viscosity of medium
Sedimentation
STOKE’S LAW
 Applicable to irregular shaped
particles of various sizes
 Particles must not be aggregated or
clumped together

24
Sedimentation

2. Pipet method
Andreasen apparatus
consisting of 550mL
vessel with a 10mL
pipet sealed in the
cylinder

25
Sedimentation
PIPET METHOD:
 The analysis is carried out by
introducing a 1 or 2% suspension of the
particles in a medium into the vessel
and brought to the 550ml mark
 The stoppered vessel is shaken to
distribute the particles uniformly
throughout the suspension and the
apparatus
 With pipet in place, the suspension is
then allowed to settle in a temperature-
controlled environment 26
Sedimentation
PIPET METHOD
 At various time intervals, 10mL samples
are withdrawn and discharge by the 2
way stopcock
 The samples are then evaporated and
weighed
 The weight of each sample residue is
therefore called the weight undersize
 The sum of the successive weights is
known as the cumulative undersize
 It may be expressed directly in weight
units or as percent of the total weight
of the final sediment 27
Sedimentation
PIPET METHOD
 DISADVANTAGES:
 it is a labor-intensive procedure
 a high level of skill is needed

28
AUTOMATIC PARTICLE COUNTERS
1. Coulter Counter
Principle: electric resistance (high ER,
big size)

2. HIAC/Royco instrument
Principle-light blockade (high
blockade, big size)
3. Gelman Counter
Principle- Faraday Tyndall Effect
Particle Volume COULTER
Measurement
COUNTER
 Change in
electric
resistance

30
Particle Volume
Measurement
S

31
Particle Shape and Surface Area

 Particle shape affects:

 The flow of and packing properties of a
powder
 Some influence on surface area

 Surfacearea per unit weight or

volume is an important in adsorption
and dissolution rate studies
32
Particle Shape and Surface Area

 PARTICLE SHAPE
 Sphere has minimum surface area per
unit volume
 More asymmetric a particle,  surface
area per unit volume
 Spherical particle is characterize by its
diameter
  asymmetric particle = difficult to
assign a diameter
33
Particle Shape and Surface Area

 SPECIFIC SURFACE
 “surface area per unit volume or per unit
weight”

34
 Methods for Determining Surface
Area
 Surface area can be computed using the
particle size distribution
 Two methods:

Adsorption Method
• amount of a gas or liquid solute that is adsorbed
onto the sample of powder to form monolayer is a
direct function of surface of sample
Air Permeability Method
• Depends on the rate at which the gas or liquid
permeates a bed of powder is related to the 35
surface area exposed to the permeant
ADSORPTION METHOD

36
37
 Pore Size

 Materials of high specific area may

have cracks and pores that adsorb
gases and vapors (water) into their
interstices
 Insoluble powdered drugs may
dissolve more or less rapidly in
aqueous medium depending upon
their absorption of moisture or air.
38
Derived Properties of Powder

Packing Densities of
Porosity Arrangement Particles

Flow
Bulkiness Compaction
Properties

39
Densities of
Particles

 Defined as weight per unit volume

 Some particles may be hard and
smooth; rough and spongy
 Types of densities:

True Granule Bulk

Density (ρ) Density (ρg) Density (ρb)
40
 True
Density
 True
density of the material itself,
w/o of voids and intraparticle pores

 Determined by displacement in
liquids in which they are insoluble
 If material is porous, it is determined
by helium densitometer

41
 True
Density HELIUM DENSITOMETER
Volume of the empty
+ Weighed powder
apparatus ( qty of helium)

Adsorbed gases are removed

+ Helium
by out gassing method

Pressure is read on a mercury Volume of He is calculated

manometer using gas laws

Vol He in empty apparatus – 42

Vol He in the powder
Granule
Density
 Determined by the displacement of
mercury, which does not penetrate at
ordinary pressures into pores smaller
than about 10μm
 Mercury because it penetrates into the
internal pores of the particles
 Volume of particles + intraparticle
spaces
43
 Bulk
Density
 Defined as mass of powder divided by
the bulk volume
 Determined from the bulk volume and
the weight of a dry powder in a
graduated cylinder

44
 Bulk
Density
 Method for bulk specific volume:
50cm3 powder cylinder is dropped
passed in Sieve #20 at 2-second interval
place in 100-mL on hard wood for 3x
grad cyl at 1 inch height

ρb = weight of
sample/ final
volume in cm3 45
 Bulk
Density
 “LIGHT pharmaceutical powders” –
LOW bulk density or large bulk
volume
 “HEAVY pharmaceutical powders” –
HIGH bulk density or small bulk
volume
 Depends on particle size distribution,
particle shape and the tendencies of
particles to adhere to one another 46
Types of volume:
True Volume/
Particle Volume (Vp) • Volume w/o voids

Granular volume • True Volume + Intraparticle

(Vg) space

•True Volume + Intraparticle space + Interparticle

Bulk volume (Vb) space
•Vg + Interparticle space

• Volume of spaces
Void volume
• Vb – Vp 48
Porosity

 “ε”
 Study of voids or empty space
 Porosity is expressed in %

49
Porosity

 Types of Porosity

Intraparticle Porosity

Interspace Porosity

Total Porosity
50
Porosity

Intraparticle Porosity

Intraparticle space
% ε Intraparticle = x 100
𝑉𝑔

𝑉𝑔 − 𝑉𝑝 𝑉𝑝
% ε Intraparticle = x 100 Or 1 - x 100
𝑉𝑔 𝑉𝑔

ρg
 % ε Intraparticle = 1- x 100
ρ 51
Porosity

Intraparticle Porosity EXAMPLE:

The granule density, ρg, of sodium

bicarbonate is 1.450 and the true
density, ρ, is 2.033. Compute for the
intraparticle porosity.

52
Porosity

Intraparticle Porosity SOLUTION:

ρg
 % ε Intraparticle = 1- x 100
ρ

1.45
 % ε Intraparticle = 1- x 100
2.033

% ε Intraparticle = 28.68%
53
Porosity

Interspace Porosity

Interparticle space
% ε Interspace = x 100
𝑉𝑏

𝑉𝑏 − 𝑉𝑔 𝑉𝑔
% ε Interspace = x 100 Or = 1 - 𝑉𝑏
x 100
𝑉𝑏

ρb
 % ε Interspace =1- x 100
ρg 54
Porosity

Total Porosity

 The porosity or voids of the powder is defined

as the ratio of the void volume to the bulk
volume of the packing
 𝜺𝒕𝒐𝒕𝒂𝒍 =
𝑰𝒏𝒕𝒓𝒂𝒑𝒂𝒓𝒕𝒊𝒄𝒍𝒆 𝒔𝒑𝒂𝒄𝒆+𝑰𝒏𝒕𝒆𝒓𝒑𝒂𝒓𝒕𝒊𝒄𝒍𝒆 𝒔𝒑𝒂𝒄𝒆
𝒙 𝟏𝟎𝟎
𝑽𝒃
𝐕𝐛 − 𝐕𝐩 Vp
 𝜺𝒕𝒐𝒕𝒂𝒍 = x 100 𝐎𝐫 = 𝟏 − x 100
𝐕𝐛 V b
ρb
 𝛆𝐭𝐨𝐭𝐚𝐥 = 𝟏 − x 100 55
ρ
Porosity

Example: Porosity

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 82.0 cm3 when placed
in a graduated cylinder.
a. Calculate the porosity
b. Compute for the void volume of the
powder 56
Porosity

Given:
True density = 3.203
Weight = 131.3g have bulk volume (Vb) of
82cm3

True volume (Vp)?

Vp = M/D
Vp = 131.3 g / 3.203
Vp = 41.0 cm3
57
Porosity

A. Porosity? B. Void Volume

𝑽𝒑 V = Vb - Vp
𝜺=𝟏 − x 100
𝑽𝒃

V = 82cm3 – 41 cm3
41.0 𝑐𝑚3
𝜺 = 1- 𝑥 100
82 𝑐𝑚3
V = 41 cm3
𝜺 = 50%
58
Porosity

Exercise: Porosity

A powder was determined to have a

density of 4.57g/cm3, weighing 125g
it was found to have a bulk volume of
78 cm3 when placed in a 100ml
graduated cylinder
a. Calculate the porosity
b. Compute for the void volume of the
powder 59
Porosity

Example: Bulk Density and Porosity

The weight of a NaI tablet was 0.3439 g

and the bulk volume was measured by
and found to be 0.0963mL. The true
density of NaI is 3.667g/mL.
a. Calculate the bulk density
b. Compute for the total porosity of
the tablet 60
Porosity

A. Bulk Density B. Total Porosity

(ρb)
ρb
𝛆𝐭𝐨𝐭𝐚𝐥 = 𝟏 − x 100
𝑊𝑒𝑖𝑔ℎ𝑡 ρ
ρb = 3.57
𝑉𝑏 𝛆𝐭𝐨𝐭𝐚𝐥 = 𝟏 − x 100
0.3439𝑔 3.667
ρb =
0.0963𝑚𝐿
𝛆𝐭𝐨𝐭𝐚𝐥 = 2.65%
ρb = 3.57g/mL
61
Porosity

Example: Total Porosity Compute for:

a. True volume
The following data apply b. Granule volume
to 1 g sample of a
granular powder: c. Bulk volume

-Volume of solid alone= d. Total Porosity

0.5mL/g e. Interspace porosity
-Volume of intraparticle f. Intraparticle
pores= 0.1mL/g porosity
-Volume of spaces
between particles=
1.6mL/g 62
Porosity

Solutions:

a. Vp = 0.5mL
b. Vg = V + Intraparticle pores

Vg = 0.5 + 0.1
Vg = 0.6mL
c. Vb = V + Intraparticle pores + spaces between
particles
Vb = 0.5 + 0.1 + 1.6
Vb= 2.2 mL 63
Porosity

d. Total Porosity f. Intraparticle porosity

𝑉𝑝 𝑉𝑝
εtotal = 1 - x 100 εintraparticle = 1 - x 100
𝑉𝑏 𝑉𝑔
𝟎.𝟓 𝟎.𝟓
εtotal = 1 - x 100 ε intraparticle = 1 - x 100
𝟐.𝟐 𝟎.𝟔
εtotal = 77.27% εintraparticle = 16.67%
e. Interspace porosity
𝑉𝑔
εinterspace = 1 - x 100
𝑉𝑏
𝟎.𝟔
εinterspace = 1 - x 100
𝟐.𝟐
64
εinterspace = 72.73%
Porosity

Exercise: Total Porosity Compute for:

a. True volume
The following data apply b. Granule volume
to 1 g sample of a
granular powder: c. Bulk volume

-Volume of solid alone= d. Total Porosity

0.5mL/g e. Interspace porosity
-Volume of intraparticle f. Intraparticle
pores= 0.2mL/g porosity
-Volume of spaces
between particles=
1.9mL/g 65
 Packing
Arrangement

 Powders beds of uniform sized spheres can

assume either one of two ideal packaging
arrangements:
a. closest or rhombohedral

b. most open, loosest or cubic packing

66
 Packing
Arrangement

 Theoretic porosity of powder of

uniform spheres:
 closest packing 26%, loosest packing 48%
 BUT particles in real powders are
neither spherical in shape nor uniform in
size
 Most powders have porosities between
30-50%
 Particles in different sizes, smaller
particles may sift between the larger to 67
give porosities below 26%
 Packing
Arrangement

 Powders containing flocculates or

aggregates, porosity is above
minimum of 48%
 Crystalline materials under pressure
have porosities less than 1%

68
Bulkiness

 Specific bulk volume

 Reciprocal of bulk density
 Important in the packaging of
powders
  particle size = Bulkiness
 Mixture of materials of different
sizes, smaller particles between large
ones =  Bulkiness
69
Bulkiness

Which is more BULKY?

A B 70
 Flow
Properties

 Powders may be free-flowing

(“dusty”) or cohesive (“sticky”)
 Factors affecting flow properties:
1. particle size
2. shape
3. porosity
4. density
5. surface texture
71
 Flow
Properties

 Small particles (>10μm) -  flow

 Poor flow brought by moisture
 drying powder   cohesiveness
 Elongated or flat particles tend to
pack loosely, giving powders high
porosity
 Free-flowing powders has high density
and low internal porosity
 BUT surface roughness may lead to poor
flow characteristics due to friction and 72

cohesiveness
 Flow
Properties

73
 Flow
Properties

 ANGLE OF REPOSE:
 Frictional forces in a loose powder
 maximum angle possible between the
surface of a pile of powder and the
horizontal plane

74
75
 Flow
Properties

 ANGLE OF REPOSE (Φ):

 If more material is added to the pile, it slides
down the sides until the mutual friction of
the particles, producing a surface at an angle
is in equilibrium with the gravitational force
𝒉
tan Φ =𝒓𝒂𝒅𝒊𝒖𝒔
 The rougher and more irregular the
surface of the particles, the higher will
be the angle of repose
76
 Flow
Properties

 Example: Solution:
tan Φ = h/radius
12 cm
tan Φ = 12cm/2.5cm
tan Φ = 4.8
Φ = tan-1(4.8)
5 cm Φ = 78.23
 What is the angle of
repose?

77
 Flow
Properties

 Example: Solution:
tan Φ = h/radius
tan Φ = 3cm/2.5cm
3 cm tan Φ = 1.2
Φ = tan-1(1.2)
5 cm Φ = 50.19
 What is the angle of
repose?

78
 Flow
Properties

 Example: Solution:
tan Φ = h/radius
tan Φ = 3cm/5.5cm
3 cm tan Φ = 0.55
Φ = tan-1(0.55)
11 cm Φ = 28.81
 What is the angle of
repose?

79
 Flow
Properties

 Example: Solution:
tan Φ = h/radius
tan Φ = 3cm/8cm
3 cm tan Φ = 0.375
Φ = tan-1(0.375)
16 cm Φ = 20.56
 What is the angle of
repose?

80
 Flow
Properties
ACCORDING TO USP:
Flow Property Angle of repose (degrees)

Excellent 25 - 30

Good 31 – 35
Fair – aid not needed 36 – 40
Passable – may hang up 41 – 45
Poor- must 46 – 55
agitate/vibrate
Very poor 56 – 65 81

Very, very poor >66

 Flow
Properties
ANGLE OF REPOSE
Which has excellent flow?

A B
82
 Flow
Properties

  angle of repose =  bulk density and

flowability

 APPLICATION:
 Ability of powders (tablets and capsule)
to flow is one of the factors involving
mixing different material to form powder
blend

83
Compaction

Drug + Small Drug + BIG

Drug particles particles 84
Compaction

 When powders are compacted under

pressure (5kg/cm2), the porosities of
the powders composed of rigid
particles (ex. Na2CO3)were higher
than the porosities of powders in
closest packing (determined by
tapping experiments)
 “DILATANT” powders – unexpected
expansion rather than contraction under 85
influence of stress
Compaction

 In case of soft and spongy particles

(ex.kaolin), particles deformed on
compression
 Behavior of powders under compression
is significant in pharmaceutical tableting
 Strength of a compressed tablet
depends on compression force and
particle size
 (crystalline): tablet strength=  particle
86
size
Compaction

 Compressibility (Carr’s) index and

Hausner Ratio are popular methods of
predicting powder flow
characteristics
 Determined by measuring both bulk
volume and tapped volume of powder
 Use 250-mL volumetric cylinder with
100g test sample.
 3 determination is recommended
-USP 27 <1174> Powder Flow 87
Compaction

 Carr’sIndex
Vo −Vf
CI = x 100%
Vo

 Hausner’s Ratio
Vo
HR =
Vf

Vo = initial volume
Vf = final volume 88
Compaction
ACCORDING TO USP:

89
 THANK YOU!!!

“The BEST VIEW

comes after the
hardest
CLIMB”
90