Micromeritics
5 – 10
It is the science and technology of small
particles. The unit of particle size used is the
micrometer (μm), micron (μ), and equal to 10-6
m Nanoparticles
Importance of Micromeritics
• Particle size plays an important role for
dosage forms (dissolution rate- increase the
surface area, decreases particle size. Therefore,
increase the solubility of a drug. It also
increases bioavailability because mas mabilis
ma dissolve, mas mabilis ma absorb. Emulsions
and suspension, smaller particle size, it helps
suspends and disperse the particle uniformly in
your liquid preparation.)
• Physical stability
• Pharmacologic response
• Flow/dissolution properties for solid
formulations
• Proper mixing of granules and powders
Size and Range of Particles in Pharmaceutical
Preparations
Granulation
1000 – 3360 (Tablet preparation)
Coarse powder
150 – 1000 (Drug powders)
Fine powder
50 – 100 (Drug powders)
Emulsions and suspension
10 – 50 (Coarse emulsions and flocculated
suspensions)
Dry powder
1 – 5 (Inhalation)
Emulsions and suspensions
0.
Nanoemulsions
0.01 – 0.5 (Colloids)
0.001 – 0.1 (Novel drug delivery systems)
Methods of Determining Particle Size
1. Optical Microscopy
• (range: 0.2 um to 100 um)
• Prasad and Wan used video recording
equipment to observe, record, store, and
retrieve particle size data from microscopic
examination of tablet excipients including
microcrystalline cellulose, Na CMC, MC.
• The microscope eyepiece is fitted with a
micrometer by which the size of the particles
may be estimated
Terms to describe particle size:
1. Feret diameter- distance between 2 tangents
on opposite sides of the particle parallel to
some fixed direction.
2. Martin diameter- the length of a line that
bisects the particle image.
3. Projected Area diameter- diameter of a circle
with the same areas as that the particle
observed perpendicularly to the surface oneach
particle rest.
Formula:
Σnd
𝑑𝑎𝑣𝑒 =
Σn
 Size Middle No. of “nd” 90 x 14.35 =1291.5
group of Value particles
110 x 3.22 = 354.2
counted “d” per
particles group 6370.6
(μm) “n”
(D X N) 6370.6
= 63.706μm
40-60 50 15 750 100
60-80 70 25 1,750
80-100 90 95 8,550
100-120 110 140 15,400 3. Sedimentation (range: 0.08 –300μm):
120-140 130 180 23,400 • The particle size in the subsieve range may be
455 49850 obtained by gravity sedimentation as expressed
49,850 by Stoke’s Law.
𝑑𝑎𝑣𝑒 = = 109.56 μm
455
18𝑛𝑜ℎ
2. Sieving (range: 40 – 9500 μm)
𝑑𝑠𝑡 = √(𝑝𝑠 − 𝑝𝑜)𝑔𝑡
• Stack of sieves is arranged in order, the
powder is placed on the top of the sieve, the
stack shaken and the quantity of powder resting
on each sieve weighed.
Sample problem:
Formula
Using the Stoke’s Eq. Calculate the particle
Σ(%retained) 𝑥 (𝑎𝑣𝑒𝑟𝑎𝑔𝑒 𝑠𝑖𝑧𝑒) diameter, dst of MgO powder (density=3.65) in
𝑑𝑎𝑣𝑒 = an aqueous medium (density 1.05) and viscosity
100
of 0.013 poise. The particles settle a distance of
Size Arithmetic No. of % Retained
24 mm in 1 hour. Remember to convert 24
group of Mean particles
mm/hr to cm/sec for the rate of settling
counted Opening per
particles (mm) group 24mm –cm = 2.4
(μm) “n”
𝟏𝟓.𝟓 𝑑𝑠𝑡
20/40 30 15.5 𝒙𝟏𝟎𝟎 =
𝟏𝟎𝟖.𝟕 0.13𝑔
14.26% 18( )(2.4𝑐𝑚)
𝑐𝑚. sec
40-60 50 25.8 23.74% = √ 6 𝑐𝑚
(3.65 − 1.05 𝑐𝑚3) (981 𝑠𝑒𝑐2)(3600 sec )
60-80 70 48.3 44.43%
80-100 90 15.6 14.35%
100-120 110 3.5 3.22%
√6.12𝑥10 − 8 = 2.47𝑥10 − 4 or 2.47 μm
108.7 100
𝑤𝑡(𝑔)
Using Andreasen Pipet.
%weight retained 𝑡𝑜𝑡𝑎𝑙 𝑤𝑡 𝑥 100
• It is a special cylindrical container designed
Σ(%retained) 𝑥 (𝑎𝑣𝑒𝑟𝑎𝑔𝑒 𝑠𝑖𝑧𝑒) such that a sample can be removed from the
100 lower portion at selected time intervals.
30 x 14.26 = 427.8 • The powder is dispersed in a nonsolvent in the
Andreasen Pipet, agitated, and 20 mL. Samples
50 x 23.74 = 1187
removed over a period of time. Each 20 mL
70 x 44.43 = 3110.1 sample dried and weighed
 Porosity or Voids ( ε )
4. Particle Volume Measurement • Is the ratio of the void volume to the bulk
volume.
• A popular instrument to measure the volume
of particles is the Coulter Counter • Suppose a nonporous powder, is placed in a
graduated cylinder:
• Principle that when a particle is suspended in
a conducting liquid passes through a small o the total volume occupied is known as
orifice, on either sides of which are electrodes, the bulk volume (Vb).
a change in electric resistance occurs.
o bulk volume = true volume + volume
of spaces between particles.
Formula:
Methods of Determining Particle Size
𝑉𝑏 − 𝑉𝑝 𝑉𝑝
• Adsorption Method – the surface area of a ε = =1−
𝑉𝑏 𝑉𝑏
sample is measured through the amount of gas
or liquid solute that is absorbed on the sample Note: Porosity is frequently expressed in
of the powder to form a monolayer. percent, ε x 100

• Air Permeability Method- the surface area is

dependent on the rate of liquid permeates on
Sample problems:
powder
1. A sample of CaO powder with a true density
Derived Properties of Powders
of 3.203 and weighing 131.2 g was found to
Volume (fundamental properties of powder) have a Vb of 82 cm3 when placed in 100mL
graduated cylinder. Calculate its porosity.
• True Volume
• Granule Volume
• Bulk Volume
Porosity
• Intraparticle Porosity
• Interspace Porosity
• Total Porosity
Density
• True Density 2. A selected powder has a true density of 3.5
g/cm3 . Experimentally, 2.5 g of the powder
• Granule Density measures 40 ml in a cylinder graduate.
• Bulk Density Calculate the true volume, void, porosity,
apparent density.
Bulkiness
Flow Properties
 𝑉𝑏−𝑉𝑔 𝑉𝑔 𝑃𝑏
ε intraparticle = =1− = 1 − 𝑃𝑔
𝑉𝑏 𝑉𝑏

Is made up of voids between the particles as

well as the pores within the particles.
𝑉𝑏−𝑉𝑝 𝑉𝑝 𝑃𝑏
ε intraparticle = = 1− = 1 − 𝑃𝑡
𝑉𝑏 𝑉𝑏

The weight of NaI tablet was 0.3439g and the

Vb was measured using caliper and found to be
Packing Arrangements: 0.0963cm3. The ρ of NaI is 3.667 g/cm3. What is
the ρb and ε total of the tablet?
• Closest packing or rhombohedral or triangle –
26% porosity, angles of 600 and 1200 are
common.
• Loosest or most open or cubic open- where
cubes are packed at 900 angles to each other
and results to 47%
Types of Densities
1. True density (ρt) – absolute density (density Sample Problems
without the volume of the pores
1. Calculate the porosity of sample Al2O3
2. Granule density (ρg) - obtained displacement having a ρ 4.0 g/cm3 when 75g of the powder
of mercury was placed in a grad. Cylinder it was found to
have a Vb of 62 cm3.
3. Bulk density (ρb) – volume including the
volume of all the pores within the sample (light
powder: low bulk density or large bulk volume.
Heavy powder – high bulk density or
low/smaller bulk volume)
𝑉𝑔−𝑉𝑝 𝑉𝑝 𝑃𝑔
ε intraparticle = =1− =1−
𝑉𝑔 𝑉𝑔 𝑃𝑡

Example: The ρ granule of NaHCO3 is 1.450 and

the ρ is 2.033 Calculate ε intraparticle. 2. If the weight of tablet is 0.2626g g and its Vb
is 0.0836ml. What is ρb? If the ρ is 3.202, what
is the porosity of the tablet?

Relative volume of the interspaces voids to the

Vb of the powder, exclusive of the intraparticle
pores.
3. The ρ of ASA is 1.37 and ρg is 1.33. what is Powder transfer through large equipment such
the porosity or % void spaces within the as hopper.
granules?

Methods of Determining Particle Size

1. Calculate the %porosity of the talc that has a
ρ of 2.7. when 324g of the powder was placed
in graduate, it occupies a Vb of 200ml.
Uneven powder flow → excess entrapped air
2. The ρ of a powder mixture is 3.203 when within powders → capping or lamination
compressed into tablet form, the ρg of the
mixture is found to be 3.138. what is the
porosity of the tablet? Methods of Determining Particle Size
Methods of Determining Particle Size Non-uniformity (segregation) in blending
Bulkiness Common manufacturing problems are
attributed to powder flow:
(increase of bulk density , the bulkiness
decreases) Powder storage: which for example result in
• Specific bulk volume caking tendencies within a vial or bag after
shipping or storage time.
• The reciprocal of bulk density(ρb)
Carr’s Compressibility index
• Increases with the decrease in particle size 𝑻𝒂𝒑𝒑𝒆𝒅 𝒅𝒆𝒏𝒔𝒊𝒕𝒚−𝒃𝒖𝒍𝒌 𝒅𝒆𝒏𝒔𝒊𝒕𝒚
𝐶𝑎𝑟𝑟 ′ 𝑠 𝑖𝑛𝑑𝑒𝑥 (%) = 𝒙 𝟏𝟎𝟎
𝒕𝒂𝒑𝒑𝒆𝒅 𝒅𝒆𝒏𝒔𝒊𝒕𝒚
• Free-flowing: characterized by dustibility
Flow description % Compressibility
• Flowability Excellent flow 5-13
o The ease with which a powder will Good 16-18
flow under a set of conditions. Fair 19-21
Poor 22-25
• Cohesiveness (sticky) Very poor 36-40
o To improve flow characteristics, Extremely poor > 40
glidants are added to granular powders.
Examples are magnesium stearate, talc Hausner Ratio
and starch
𝑇𝑎𝑝𝑝𝑒𝑑 𝑑𝑒𝑛𝑠𝑖𝑡𝑦
Common manufacturing problems are 𝐻𝑎𝑢𝑠𝑛𝑒𝑟 𝑅𝑎𝑡𝑖𝑜 = 𝐵𝑢𝑙𝑘 𝑑𝑒𝑛𝑠𝑖𝑡𝑦
attributed to powder flow:
Interpretation Hausner Ratio
 Good <1.25
Fair to passable 1.25-1.50
Lab
Poor >1.5
Micromeritics
Angle of Repose ▹ Is the science and technology of small
ℎ𝑒𝑖𝑔ℎ𝑡
𝑎𝑛𝑔𝑙𝑒 𝑜𝑓 𝑟𝑒𝑝𝑜𝑠𝑒 = 𝑎𝑟𝑐 𝑡𝑎𝑛 𝑟𝑎𝑑𝑖𝑢𝑠 = particles.
2𝑥ℎ𝑒𝑖𝑔ℎ𝑡
𝑎𝑟𝑐 𝑡𝑎𝑛 𝑑𝑖𝑎𝑚𝑒𝑡𝑒𝑟 ▹ As particle size decreases, surface area
increases.
Interpretation Angle of repose
▹ In the area of tablet and capsule manufacture,
Excellent <25
Good 25-30 control of the particle size is essential in
achieving the necessary flow properties and
Fair 30-40
proper mixing of granules and powders.
Poor >40

Sample Problem Application of Micromeritics

The following data apply to a 2.5g sample of a 1. Release and Dissolution

granular powder
• Volume of solid alone= 0.5cm3 /1 g
• Volume after tapping = 1.5 cm3
• Volume of intraparticle pores= 0.3 cm3 / 0.5 g
• Volume of spaces between particles = 2.0 cm3
/ 2g
Solve Vt, Vg, Vb, Pt, Pg, Pb, Eintra, Einter, Etotal,
bulkiness, HR, CCI? Interpret the values for HR
and CCI
2. Absorption and drug action
3. Physical stability
4. Dose uniformity
Methods for Particle Size Determination
1. Optical microscopy (0.2 – 100 µm)
2. Sieving (40 – 9500 µm)
3. Sedimentation (0.08 – 300 µm)
4. Particle volume measurement (0.5 - 300 µm)

Range of Particle Sizes

Particle size Method
1 µm Electron microscope,
ultracentrifuge,
adsorption
1 – 100 µm Optical microscope,
sedimentation,
coulter
counter, air
permeability
 >50 µm Sieving 𝑀
𝑏𝑢𝑙𝑘 𝑑𝑒𝑛𝑠𝑖𝑡𝑦 =
𝑉𝑜
Disadvantage of Microscopic methods 𝑀
𝑇𝑎𝑝𝑝𝑒𝑑 𝑑𝑒𝑛𝑠𝑖𝑡𝑦 =
𝑉𝑓
1. The diameter is obtained from only two
dimensions of the particle. Applications

2. The number of particles that must be
counted (300 – 500) to obtain a good estimate
of the distribution makes somewhat slow and
tedious.
Classification of Powders using Sieve Method
1. Decides the size of the capsule based on bulk
and tapped volume of a given sample
2. Helps to decide the proper size of a container
or packing material

Classification Sieve no. % that passes

through
Coarse 40 60
powder
Moderately 60 60
coarse
Fine 80 100
Very fine 120 100

Particle Volume Measurement

1. Electrical stream sensing zone method
(Coulter counter)
2. Laser light scattering methods
Advantages:
1. Particle size ranging from 0.5 – 500 microns
2. Gives number distribution, particle volume
measure and can be converted to diameter.
3. Accurate, sensitive, and fast technique.
4. 4000 particles per second can be counted.
Disadvantage:
1. Expensive
Derived Properties of Powders
Density

▹ Apparent bulk density

▹ Tapped density
I. Rheology
Rheo (to flow) and logos (science: to study)
Describes the flow characteristics of liquid and
deformation of solids
Viscosity (η) – resistance of a fluid to flow.
The higher the viscosity the greater the
resistance
Classification of materials:
Newtonian – which follows the Newton’s law
of flow.
Non-Newtonian – substances that fail to follow
Newton’s equation of flow.
Newtonian system
The higher the η of a liquid, the greater the
force/unit area (shearing stress) required to
produce a certain rate of shear.
F’/A = η dv/dr
Where F’/A = F; and dv/dr = G
η = F/G
𝑑𝑦𝑛𝑒𝑠 . 𝑐𝑚 𝑔 . 𝑐𝑚/𝑠2𝑥𝑠
η = F’dr = 𝑐𝑚2 . = =
𝑐𝑚/𝑠 𝑐𝑚2
η = poise
The unit of η is poise
defined as the shearing force required to
produce a velocity of 1 cm/sec between two
parallel planes of liquid each 1 cm2 in area and
separated by a distance of 1 cm
Cgs unit are dyne sec/cm2 or g/cm sec
Fluidity (φ) – reciprocal of η.
1/η
Kinematic and Relative viscosity
Kinematic viscosity: absolute viscosity divided
by the density of the liquid at a definite
temperature.
ηkin = η/ρ
Unit: stoke (s) and centistoke (cs)
Relative viscosity (ηrel): viscosity of the sample
divided by viscosity of standard
Water = 1.0019 cp @ 20
Non-Newtonian System
I. Plastic Flow
• Does not pass through the origin (point)
but rather intersects the shearing stress
axis at a point referred to as the yield
value
• Does not begin to flow until shearing
stress, corresponding to the yield value,
is exceeded.
Non-Newtonian System
• Associated with the presence of
flocculated particles in concentrated
suspension.
• f is present because of the contacts
𝑔
between adjacent particles, which must
𝑐𝑚 . 𝑠
be broken down before flow can occur.
II. Pseudoplastic flow
• The η of a pseudoplastic substance
decreases with increasing rate of shear.
• As the shearing stress is increased, the
normally disarranged molecules begin
to align their long axes in the direction
of flow.
• This orientation reduces the internal
resistance of the material and allows a
greater rate of shear at each successive
shearing stress
III. Dilatant flow
• Such systems actually increase in
volume when sheared.
• When stress is removed, it returns to its
original state of fluidity.
• A rest, the particles are closely packed
with the interparticle volume or voids,
being at a minimum.
Antithixotropy
• Shear thickening material
• Increases viscosity with increase rate of
shear
• Magnesia magma at shear rates of >
30/sec
• Rheopexy – a phenomenon in which a
solid forms a gel readily when gently
shaken or otherwise sheared that when
allowed to form the gel while the
material is kept at rest
Thixotropy
Pseudoplastic material (shear thinning)
• This indicates a breakdown of structure
that does not reform immediately when
the stress is removed or reduced.
• This phenomenon is called thixotropy –
an isothermal and comparatively slow
recovery, on standing of material, of a
consistency lost through shearing.
• At rest – system is rigid –
resembles gel
• As shear is applied and flow
starts, the structure begins to
breakdown as the points of contacts are
disrupted and the particles become
aligned
• Gel-to-sol transformation, upon
removal of the stress, the structure
starts to reform
Determination of Rheologic Properties
Capillary Viscometer
• The η of a Newtonian liquid maybe
determined by measuring the time
required for the liquid to pass between
two marks as it flows by gravity through
a vertical capillary tube, Ostwald
viscometer.
• Eq: η1/η2 = t1ρ1/t2
Falling sphere viscometer
• A glass or steel ball rolls down to an
almost vertical glass tube containing the
test liquid at a known constant
temperature. The rate at which a ball of
a particular density and diameter falls is
an inverse function of the viscosity of
the sample
• Hoeppler viscometer
• Η = t(Sb-Sf)B
• 0.5 - 200,000 poise
• t nlt 30 secs
Cup and Bob
• The sample is sheared in the space
between the outer wall of the bob and
the inner wall of the cup into which the
bob fits
• Many instruments differ mainly in
whether the torque (force acting to
produce rotation) set up in the bob
results from the cup or from the bob
being caused to revolve
Couette type – cup is rotated, the resultant
torque is proportional to the viscosity of the
sample
• MacMichael viscometer
Searle type – stationary cup, rotating bob
• Rotovisco
• Stormer
• Brookfield
Cone and Plate
• Ferranti-Shirley
• The sample is placed at the center of
the plate, under the cone
 • The cone is driven by a variable-speed
motor and the sample is sheared
between the stationary plate and the
rotating cone
Viscosity
Viscosity Coefficients
▹ Viscosity coefficients can be defined in two
ways:
▸ Dynamic or Absolute viscosity

▹ A quantitative measure of a fluid’s resistance ▸ Kinematic Viscosity

to flow. ▸ Relative Viscosity
▹ It is defined as the internal friction of fluid.
Non-Newtonian Fluids Absolute Viscosity
A. Shear-dependent Viscosity 𝐹
𝑛=
𝐺
1. Plastic
F = shear stress
2. Pseudoplastic
G = shear rate
3. Dilatant
Units: Poise, centipoise (cP)
B. Time-dependent Viscosity
Kinematics Viscosity
1. Thixotropy
𝑛
2. Rheopexy 𝐾=
𝑝
Shear-dependent Viscosity n = absolute viscosity
Pseudo Plastics p = density of the substance in g/cm3
▹ Display a decreasing viscosity with an Units: Stokes, centistokes (cS)
increasing shear rate.
▹ Also called shear thinning
Relative Viscosity

Dilatant ▹ Ratio of the viscosity of a solution to the

viscosity of the solvent
▹ Display an increasing viscosity with an
increasing shear rate. ▹ unitless

▹ Also called shear thickening.

Plastic (Bingham)
▹ Behave as a solid under static conditions.
Time-dependent Viscosity
▹ Thixotropy (gel-sol transformation)
Sample Problem
1. An Ostwald viscometer was used to measure
acetone, which was found to have a viscosity of
0.313 cp at 25ºC. Its density at 25ºC is 0.788
g/cm3. What is the kinematic viscosity of
acetone?

▹ Rheopexy (sol-gel transformation)

 Factors Affecting Viscosity

▹ Temperature

▹ Particle Size

▹ Concentration

▹ Attractive Forces

2. Water is ordinarily used as a standard for

viscosity of liquids. Its viscosity at 25ºC is 0.8904
cp. What is the viscosity of acetone relative to
that of water (relative viscosity) at 25ºC?

Sample Problem

▹ The time required for acetone to flow

between the two marks on the capillary
viscometer was 45 sec, and for water the time
was 100 sec, at 25ºC. The density of acetone is
0.786 g/mL and that of water is 0.997 g/mL at
25ºC. The viscosity of water is 0.8904 cp at this
temperature. Calculate the viscosity of acetone