Micromeritics

Micromeritics
Dr. Basavaraj K. Nanjwade
M. Pharm., Ph. D
Department of Pharmaceutics
Faculty of Pharmacy
Omer Al-Mukhtar University
Tobruk, Libya.
E-mail: nanjwadebk@gmail.com
2014/02/23
Faculty of Pharmacy, Omer Al-Mukhtar

University, Tobruk, Libya.
CONTENTS
1.
2.
3.
4.
Particle Size and Size Distribution.

Methods for determining particle size.
Density and Flow properties of powders.
References.
2014/02/23

Micromeritics
Definition: It is the science and technology of
small particles.
The unit of particle size used in the
micrometer (m), micron () and equal to 10 -6
m.
As particle size decreases , area increases
2014/02/23

Micromeritics
2014/02/23

Micromeritics
Micromeritics is the science and technology of small
particles. Knowledge and control of the size and the
size range of particles are of significant importance in
pharmacy because the size and surface area of a
particle related to the physical, chemical and
pharmacologic properties of a drug.
The particle size of a drug can affect its release from
dosage forms that are administered orally,
parenterally, rectally and topically.
2014/02/23

Micromeritics
In the area of tablet and capsule manufacture,
control of the particle size is essential in
achieving the necessary flow properties and
proper mixing of granules and powders.
2014/02/23

Particle Size and

Size Distribution
In a collection of particles of more than one size, two
properties are important, namely.
1. The shape and surface are of the individual particles.
2. The particle size and size distributions (The size
range and number or weight of particles).
2014/02/23

Particle Size
The size of a sphere is readily expressed in terms of its
diameter.
The Surface diameter, ds, is the diameter of a sphere having
the same surface area as the particle.
The Volume diameter, dv, is the diameter of a sphere having
the same volume as the particle.
The Projected diameter, dp, is the projected diameter of a
sphere having the same observed area as the particle.
The Stokes diameter, dst, is the diameter which describes an
equivalent sphere undergoing sedimentation at the same rate
as the asymmetric particle.
2014/02/23

Particle Size
Any collection of particles is usually polydisperse. It
is therefore necessary to know not only the size of a
certain particle, but also how many particles of the
same size exist in the sample.
Thus, we need an estimate of the size range present
and the number or weight fraction of each particle
size.
This is the particle-size distribution and from it we
can calculate an average particle size for the sample.
2014/02/23

Particle Size Distribution

When the number or weight of particles lying within
a certain size range is plotted against the size range or
mean particle size, a so-called frequency distribution
curve is obtained.
This is important because it is possible to have two
samples with the same average diameter but different
distributions.
2014/02/23

10
Micromeritics Applications
1.
2.
3.
4.
Release and dissolution.

Absorption and drug action.
Physical stability.
Dose uniformity.
2014/02/23

11
Release and dissolution

Particle size and surface area influence the
release of a drug from a dosage form.
Higher surface area allows intimate contact of
the drug with the dissolution fluids in vivo and
increases the drug solubility and dissolution.
2014/02/23

12
Absorption and drug action

Particle size and surface area influence the
drug absorption and subsequently the
therapeutic action.
Higher the dissolution, faster the absorption
and hence quicker and greater the drug action.
2014/02/23

13
Physical stability
The particle size in a formulation influences
the physical stability of the suspensions and
emulsions.
Smaller the size of the particle, better the
physical stability of the dosage form.
2014/02/23

14
Dose uniformity
Good flow properties of granules and powders
are important in the manufacturing of tablets
and capsules.
2014/02/23

15
Methods for determining

particle size
Many methods available for determining particle size
such as optical microscopy, sieving, sedimentation
and particle volume measurement.
1. Optical microscopy (range: 0.2-100 m).
2. Sieving (range: 40-9500 m).
3. Sedimentation (range: 0.08-300 m).
4. Particle volume measurement (range: 0.5-300 m).
2014/02/23

16
Range of particle sizes

A guide to range of particle sizes applicable to each
method is
Particle size
1 m
1 100 m
50 m
2014/02/23
Method
Electron microscope,
ultracentrifuge, adsorption
Optical microscope,
sedimentation, coulter
counter, air permeability
Sieving

17
Optical microscopy
(range: 0.2-100 m)
The microscope eyepiece is fitted with a micrometer by

which the size of the particles may be estimated.
2014/02/23

18
Optical microscopy
(range: 0.2-100 m)
According to the optical microscopic method, an
emulsion or suspension is mounted on ruled
slide on a mechanical stage.
The microscope eyepiece is fitted with a
micrometer by which the size of the particles can
be estimated.
The ordinary microscope used for measurement
the particle-size in the range of 0.2 to about 100
m.
2014/02/23

19
Disadvantage of
microscopic method
1. The diameter is obtained from only two
dimensions of the particle.
2. The number of particles that must be counted
(300-500) to obtain a good estimation of the
distribution makes the method somewhat
slow and tedious.
2014/02/23

20
Sieving
(range: 40-9500 m)
Standard size sieves are
available to cover a wide
range of size.
These sieves are designed to
sit in a stack so that material
falls through smaller and
smaller meshes until it
reaches a mesh which is too
fine for it to pass through.
2014/02/23

21
Sieving
(range: 40-9500 m)
The
stack
of
sieves
is
mechanically shaken to promote
the passage of the solids.
The fraction of the material
between pairs of sieve sizes is
determined by weighing the
residue on each sieve.
The result achieved will depend on
the duration of the agitation and
the manner of the agitation.
2014/02/23

22
Sedimentation
(range: 0.08-300 m)
By
measuring
the
terminal settling velocity
of particles through a
liquid medium in a
gravitational centrifugal
environment
using
Andreasen appartus.
2014/02/23

23
Particle volume measurement

(range: 0.5-300 m)
In this type of machine the powder is suspended in an
electrolyte solution.
This suspension is then made to flow through a short
insulated capillary section between two electrodes
and the resistance of the system is measured.
When a particle passes through the capillary there is a
momentary peak in the resistance, the amplitude of
the peak is proportional to the particle size.
Counting is done by a computer.
2014/02/23

24
Particle volume measurement

(range: 0.5-300 m)
2014/02/23

25
Density of powders
Density is defined as weight per unit volume
(W/V).
During tapping, particles gradually pack more
efficiently, the powder volume decreases and the
tapped density increases.
2014/02/23

26
Types of Density
1. True density: The true density or absolute
density of a sample excludes the volume of
the pores and voids within the powder
sample.
2. Bulk density: The bulk density value
includes the volume of all of the pores within
the powder sample.
2014/02/23

27
Flow properties of powders

Powders may be free-flowing or cohesive (Sticky).
Many common manufacturing problems are attributes to
powder flow.
1. Powder transfer through large equipment such as hopper.
2. Uneven powder flow excess entrapped air within
powders capping or lamination.
3. Uneven powder flow increase particles friction with
die wall causing lubrication problems and increase dust
contamination risks during powder transfer.
2014/02/23

28
2014/02/23

29

5. Powder storage, which for example result in
caking tendencies within a vial or bag after
shipping or storage time.
6. Separation of small quantity of the powder
from the bulk-specifically just before the
creation of individual doses such as during
tableting, encapsulation and vial filling which
affect the weight uniformity of the dose (under
or over dosage).
2014/02/23

30
Powder flow problems
2014/02/23

31

Tests to evaluate the flowability of a powder.
1.Carrs compressibility index.
2.Hausner ratio.
3.The angle of repose ().
2014/02/23

32
Carrs compressibility
index
A volume of powder is filled into a graduated glass
cylinder and repeatedly tapped for a known
duration. The volume of powder after tapping is
measure.
Tapped density- Poured or bulk density
Carrs index (%)=

X 100
Tapped density
Bulk density= weight/bulk volume

Tapped density=weight/true volume
2014/02/23

33
Carrs compressibility index

Relationship between powder flowability and % compressibility
Flow description
% Compressibility
Excellent flow
5 15
Good
16 18
Fair
19 21
Poor
22 35
Very Poor
36 -40
Extremely poor
40
2014/02/23

34
Hausner ratio
Tapped density
Hausner ratio =
Poured or bulk density
Hausner ratio
friction:
was
related
to
interparticle
Value less than 1.25 indicates good flow

(=20% Carr).
2014/02/23

35
Hausner ratio
The powder with low interparticle friction, such as
coarse spheres.
Value greater than 1.5 indicates poor flow (= 33%
Carrs Compressibility Index)).
More cohesive, less free-flowing powders such as
flakes.
Between 1.25 and 1.5 added glidant normally
improves flow.
1.5 added glidant doesnt improve flow.
2014/02/23

36
The angle of repose ()

The sample is poured onto the
horizontal surface and the angle
of the resulting pyramid is
measured.
The user normally selects the
funnel orifice through which the
powder flows slowly and
reasonably constantly.
2014/02/23

37
The angle of repose ()

1.
2.
3.
4.
Angle of repose less than 20 (Excellent flow).

Angle of repose between20-30 (Good flow).
Angle of repose between 30-40 (Pass flow).
Angle of repose greater than 40 (Poor flow).
The rougher and more irregular the surface of

the particles, the higher will be the angle of
repose.
2014/02/23

38
Factors affecting the flow

properties of powder
2014/02/23

39

1. Alteration of Particles size & Distribution
2. Alteration of Particle shape & texture
3. Alteration of Surface Forces
4. Formulation additives (Flow activators)
2014/02/23

40

Alteration of Particles size & Distribution
There is certain particle size at which powders flow
ability is optimum.
Coarse particles are more preferred than fine ones as
they are less cohesive.
The size distribution can also be altered to improve
flowability by removing a proportion of the fine
particle fraction or by increasing the proportion of
coarser particles such as occurs in granulation.
2014/02/23

41

Alteration of Particle shape & texture
Particles Shape
Generally, more spherical particles have better flow
properties than more irregular particles.
Spherical particles are obtained by spray drying, or
by temperature cycling crystallization.
2014/02/23

42

Alteration of Particle shape & texture
Particles texture
Particles with very rough surfaces will be
more cohesive and have a greater tendency to
interlock than smooth surfaced particles.
2014/02/23

43

Alteration of Surface Forces
Reduction of electrostatic charges can improve powder flowability.
Electrostatic charges can be reduced by altering process conditions
to reduce frictional contacts.
Moisture content of particle greatly affects powders flowability.
Adsorbed surface moisture films tend to increase bulk density and
reduce porosity.
Drying the particles will reduce the cohesiveness and improve the
flow.
Hygroscopic powders stored and processed under low humidity
conditions.
2014/02/23

44

Formulation additives (Flow activators)
Flow activators are commonly referred as a
glidants.
Flow activators improve the flowability of
powders by reducing adhesion and cohesion.
e. g. Talc, maize starch and magnesium stearate.
2014/02/23

45
Derived properties of
powders
2014/02/23

46
References
1. Text book of Physical Pharmaceutics by CVS
Subramanyam.
2. Text book of Physical Pharmacy By Albert
Martin.
3. www.google.com.
2014/02/23

47
Questions?
2014/02/23

48
E-mail: nanjwadebk@gmail.com
2014/02/23

49

Micromeritics

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Micromeritics

Uploaded by

Copyright:

Available Formats

Micromeritics

Dr. Basavaraj K. Nanjwade

Faculty of Pharmacy, Omer Al-Mukhtar

Particle Size and Size Distribution.

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Particle Size and

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Particle Size Distribution

Faculty of Pharmacy, Omer Al-Mukhtar

Release and dissolution.

Faculty of Pharmacy, Omer Al-Mukhtar

Release and dissolution

Faculty of Pharmacy, Omer Al-Mukhtar

Absorption and drug action

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Methods for determining

Faculty of Pharmacy, Omer Al-Mukhtar

Range of particle sizes

Faculty of Pharmacy, Omer Al-Mukhtar

The microscope eyepiece is fitted with a micrometer by

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Particle volume measurement

Faculty of Pharmacy, Omer Al-Mukhtar

Particle volume measurement

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

Flow properties of powders

Faculty of Pharmacy, Omer Al-Mukhtar

Flow properties of powders

Faculty of Pharmacy, Omer Al-Mukhtar

Flow properties of powders

Faculty of Pharmacy, Omer Al-Mukhtar

Powder flow problems

Faculty of Pharmacy, Omer Al-Mukhtar

Flow properties of powders

Faculty of Pharmacy, Omer Al-Mukhtar

Carrs index (%)=

Bulk density= weight/bulk volume

Faculty of Pharmacy, Omer Al-Mukhtar

Carrs compressibility index

Faculty of Pharmacy, Omer Al-Mukhtar

Value less than 1.25 indicates good flow

Faculty of Pharmacy, Omer Al-Mukhtar

Faculty of Pharmacy, Omer Al-Mukhtar

The angle of repose ()

Faculty of Pharmacy, Omer Al-Mukhtar

The angle of repose ()

Angle of repose less than 20 (Excellent flow).