TITLE:
Sieving
OBJECTIVES:
1.
To determine the particle size of
lactose and microcrystalline cellulose (MCC).
2.
To determine the size distribution of
lactose and microcrystalline cellulose (MCC).
DATE OF EXPERIMENT:
22nd November 2016
INTRODUCTION:
The particle size
distribution is defined via the mass or volume of particles. Sieving is
probably the most frequently method used to analysis the particle size because
the equipment, analytical procedure, and basic concepts are simple. Sieving is
the oldest and best-known method for particle size determination which commonly
used to break down agglomerates and determine the size and size distribution of
a particular powder. Sieve analysis (or gradation test) is used to divide the
particulate material into size fractions and then to determine the weight of
these fractions. By this way a relatively broad particle size spectrum can be
analysed quickly and reliably.
A sieve analysis can be
performed on any type of non-organic or organic granular materials including
sands, crushed rock, clays, granite, feldspars, coal, soil a wide range of
manufactured powders, grain and seeds, down to a minimum size depending on the
exact method. During sieving the sample is subjected to horizontal or vertical
movement. This causes a relative movement between the particles and the sieve;
depending on their size, the individual particles either pass through the sieve
mesh or are retained on the sieve surface. The particles passing through the
sieve mesh are determined by the ratio of the particle size to the sieve
openings, the orientation of the particle and the number of encounters between
the particle and the mesh openings.
Sieve analyses in the
laboratory and for quality assurance are carried out with sieve shakers. Modern
sieve shakers are characterized by the fact that their mechanical parameters,
such as sieving time and amplitude or speed, are carried out with exact
reproducibility. In the laboratory a differentiation is made between horizontal
sieve shakers and throw-action sieve shakers (vibratory sieve shakers).
In this practical, students
use different sieves as standardized by the IS code and stacking them on top of
one another in descending order (largest diameter to the smallest, from top to
bottom). Then, students placing the test powder on the top sieve and pass
aggregates through them and thus collect different sized particles left over
different sieves. The two excipients used in tablet formulations, namely
lactose and microcrystalline cellulose (MCC). Using sieve shaker, the particle
size and size distribution of both powders are determined.
LIST OF APPARATUS:
Sieve nest
Spatula
Weighing boats
Weighing machine
LIST OF MATERIALS:
Lactose
Microcrystalline
cellulose (MCC)
PROCEDURE:
1.
100g of lactose was weighed by using
weighing machine.
2.
The sieve nest was prepared in
descending order (largest diameter to the smallest, from top to bottom).
3.
Lactose was placed at the uppermost
sieve.
4.
The sieving machine was run for 10
minutes.
5.
After the sieving process finished, the
weights of different sizes of lactose collected at every sieve were weighed.
6.
A histogram was plotted for the
distribution of particle size of lactose.
7.
Step 1-6 were repeated by prolonged the
time to 20 minutes.
8.
Step 1-7 were repeated by using MMC
RESULT:
Lactose (10 minutes)
Sieve
Diameter (µm)
|
Particle
Size (µm)
|
Mass
of Lactose Retained in the Sieve (g)
|
Percentage
of Lactose Retained (%)
%)
|
Cumulative
Percentage Retained (%)
|
Percentage
of passing (%) (100%-cumulative percentage retained)
|
<53
|
0<X≤53
|
6.2178
|
6.2178
|
6.2178
|
93.7822
|
53
|
53<X≤150
|
2.6130
|
2.6130
|
8.8308
|
91.1692
|
150
|
150<X≤212
|
0.0672
|
0.0672
|
8.8980
|
91.1012
|
212
|
212<X≤300
|
8.9177
|
8.9177
|
17.8157
|
82.1843
|
300
|
300<X≤500
|
8.6832
|
8.6832
|
26.4989
|
73.5011
|
500
|
500<X
|
71.9801
|
71.9801
|
98.4796
|
1.5204
|
Lactose (20 minutes)
Sieve
Diameter (µm)
|
Particle
Size (µm)
|
Mass
of Lactose Retained in the Sieve (g)
|
Percentage
of Lactose Retained (%)
%)
|
Cumulative
Percentage Retained (%)
|
Percentage
of passing (%) (100%-cumulative percentage retained)
|
<53
|
0<X≤53
|
13.8096
|
13.8096
|
13.8096
|
86.1904
|
53
|
53<X≤150
|
0.0766
|
0.0766
|
13.8862
|
86.1138
|
150
|
150<X≤212
|
2.5205
|
2.5205
|
16.4067
|
83.5933
|
212
|
212<X≤300
|
6.2933
|
6.2933
|
22.7000
|
77.3000
|
300
|
300<X≤500
|
47.1532
|
47.1532
|
69.8532
|
30.1468
|
500
|
500<X
|
27.9594
|
27.9594
|
97.8126
|
2.1874
|
MMC (10 minutes)
Sieve
Diameter (µm)
|
Particle
Size (µm)
|
Mass
of MMC Retained in the Sieve (g)
|
Percentage
of MMC Retained (%)
%)
|
Cumulative
Percentage Retained (%)
|
Percentage
of passing (%) (100%-cumulative percentage retained)
|
<53
|
0<X≤53
|
9.0179
|
9.0179
|
9.0179
|
90.9821
|
53
|
53<X≤150
|
50.6871
|
50.6871
|
59.7050
|
40.2950
|
150
|
150<X≤212
|
4.9990
|
4.9990
|
64.7040
|
35.2960
|
212
|
212<X≤300
|
0.1148
|
0.1148
|
64.8188
|
35.1812
|
300
|
300<X≤500
|
0.0485
|
0.0485
|
64.8673
|
35.1327
|
500
|
500<X
|
0.0043
|
0.0043
|
64.8716
|
35.1284
|
MMC (20 minutes)
Sieve
Diameter (µm)
|
Particle
Size (µm)
|
Mass
of MMC Retained in the Sieve (g)
|
Percentage
of MMC Retained (%)
%)
|
Cumulative
Percentage Retained (%)
|
Percentage
of passing (%) (100%-cumulative percentage retained)
|
<53
|
0<X≤53
|
9.9029
|
9.9029
|
9.9029
|
90.0971
|
53
|
53<X≤150
|
44.4114
|
44.4114
|
54.3134
|
45.6857
|
150
|
150<X≤212
|
6.9248
|
6.9248
|
61.2391
|
38.7609
|
212
|
212<X≤300
|
3.1510
|
3.1510
|
64.3901
|
35.6099
|
300
|
300<X≤500
|
3.1839
|
3.1839
|
67.5740
|
32.4260
|
500
|
500<X
|
5.8545
|
5.8545
|
73.4285
|
26.5715
|
QUESTION:
1. What are the average particle size for both
lactose and MCC?
The
average particle size for lactose is bigger than 500µm while MCC is in the
range of 53µm - 150µm since the percentage of lactose and MCC retained in the
respective sieve is the highest.
2. What other method can you use to determine
the size of particle?
I. Dynamic light scattering techniques
(DLS)
DLS
is one of the most popular light scattering techniques because it allows
particle sizing down to 1 nm diameter. Typical applications are emulsions,
micelles, polymers, proteins, nanoparticles or colloids. These sample are
illuminated by a laser beam and the fluctuations of the scattered light are
detected at a known scattering angle θ by a fast photon detector. Simple DLS
instruments that measure at a fixed angle can determine the mean particle size
in a limited size range. More elaborated multi-angle instruments can determine
the full particle size distribution.
II. Laser light scattering techniques
The
laser light scattering method is used in the wet and dry samples measuring 10
nanometres to 5 millimetres. The central idea in laser diffraction is that a
particle will scatter light at an angle determined by that particle’s size.
Larger particles will scatter at small angles and smaller particles scatter at
wide angles. A collection of particles will produce a pattern of scattered
light defined by intensity and angle that can be transformed into a particle
size distribution result.
III. Sedimentation techniques
Sedimentation
techniques of particle size determination are based on the settling behaviour
of particles motion through the fluid in response to the forces acting on them:
these forces can be due to gravity, centrifugal acceleration, or
electromagnetism. This method depends on the fact that the terminal velocity of
a particle in a fluid increases with size. However, there are some
disadvantages using this method. The sample used must be dispersed in a liquid
medium. Some particles may (partially or fully) dissolve in the medium altering
the size distribution, requiring careful selection of the dispersion media.
Density is highly dependent upon fluid temperature remaining constant. X-Rays
can be used in this method but it will not count carbon (organic) particles.
IV. Microscopy
Microscopy
is the technical field of using microscopes to view objects and areas of
objects that cannot be seen with the naked eye (objects that are not within the
resolution range of the normal eye). There are three types of microscopy:
optical, electron, and scanning probe microscopy. Microscopy is being
considered as an absolute measurement of particle size because it able to
examine each particle individually. It can distinguish aggregates from single
particles. When coupled to image analysis computers each field can be examined,
and a distribution obtained. For a statistically valid analysis, millions of
particles must be measured. This is impossibly arduous when done manually, but
automated analysis of electron micrographs is now commercially available.
V. Electrical Property Techniques
Instrument
measures particle volume which utilizes the Coulter Principle to detect
particles via electrical zone sensing regardless of the nature or optical
properties of the particle. The number and size of particles suspended in an
electrolyte is determined by causing them to pass through an orifice an either
side of which is immersed an electrode. The changes in electric impedance
(resistance) as particles pass through the orifice generate voltage pulses
whose amplitude are proportional to the volumes of the particles. It is an
ideal tool for detecting and counting a wide variety of particles such as
mammalian cells, bacteria, yeast, abrasives, toner particles, cell aggregates,
spheroids and even large protein aggregates. In addition to counting particle
density the this instruments also determines the particle volume and shape.
Change in cell volume, for example, is an important factor involved in many
biological processes such as Cell Growth, Cell Cycles, Cell Death, Compensation
for Osmotic Stress, Pathogenesis and Phagocytosis.
3. What are the importance of particle size in a
pharmaceutical formulation?
The
particle size distribution of active ingredients and excipients is an important
physical characteristic of the materials used to create pharmaceutical
products. The size, distribution and shape of the particles can affect bulk
properties, product performance, processability, stability and appearance of
the end product. This is directly related to drug dissolution and drug
solubility. According to Noyes-Whitney equation, dissolution rate is directly
proportional to particle surface area. In suspensions, the physical
characteristics of the fluid and the size of particles both have an effect on
precipitation and aggregation. Smaller solid particles suspended in the liquid
will be more uniform and no agglomerates will be formed. Stability can also
depend on the balance of the repulsive and attractive forces that exist between
particles as they approach one another. If the particles have little or no
repulsive force then eventually there will be some manifestation of this
instability, such as aggregation. Stability is an important issue because if
the active ingredient settles there is a greater chance of non-uniform
delivery. Stokes' law relates settling velocity to the physical characteristics
of the fluid and the size of particles in the suspension. The relationship here
is a strong one: velocity correlates with the square of particle diameter. For
suspension stability, a very low settling velocity is preferable and is more
easily achieved with finer particles. This can increase the uniformity and
efficacy of drugs produced. Besides, smaller size of solid particles will have
larger surface area to come into contact with the medium. This can ensure that
the medicine produced can dissolve easily in the body system and function
effectively when consumed. Furthermore, when the drugs are injected into the
body system, small particle size can ensure that the drug particles will not
block the blood vessels.
DISCUSSION:
Particle
size analysis is a particle size measurement, using variety of name of the
technical procedure or laboratory techniques which determine the range of
particle size or the average particle size of the size in the powder or liquid
form. In this experiment, the sieve method is used.
In
order to carry out sieving, sieve nest has to be prepared and they are arranged
in descending order (from the largest diameter to the smallest diameter)
because sieve nest involve a nested column of sieves with wire mesh cloth
(screen). The granular materials used in this experiment are lactose and
microcrystalline crystal (MCC). The first step of the experiment was placing
the 100g of lactose powder at the uppermost sieve nest. The sieve shaker is
then started and the sieving process is carried out for 10 minutes. Later, the
lactose powder obtained from each sieve is measured. The experiment was then
repeated by sieving lactose for 10 minutes MMC for 10 and 20 minutes. The
principle used to determine the particle size is that particles that cannot
pass through a particular sieve nest has larger particle size compared to the
diameter of the sieve nest. For example, particles that cannot pass through
sieve with diameter 150µm but can pass through sieve with diameter 53µm has
particle size range between 53µm and 150µm.
From
the result obtained, it shows that most particles size of lactose after sieving
for 10 minutes are in the range of bigger than 500µm (7109801%) followed by
range of 212 – 300µm (8.9177%) and 300-500µm (8.6832%) respectively while for
20 minutes are in range of 300-500µm (4701352%) followed by range of bigger
than 500µm (27.9594 %) and smaller than 53µm (13.8096%) respectively. While as
for sieving of MCC for 10 minutes, most particles size are in the range of 53 –
150µm (50.6871%) followed by less than 53 µm (9.0179%) and a range of 150 – 212µm
(4.9990%) while for 20 minutes are in range of 53 - 150µm (44.4114) followed by
range of less than 53µm (9.9029 %) and 150-212µm ( 6.9248 %)respectively.
The
particle size of lactose is estimated to be bigger than 500µm because the sum
of percentage of lactose retained for both 10 and 20 minutes at sieve with
diameter 500µm is the highest. The particle size of MCC is estimated to be
between 53µm and 150µm because the percentage of MCC retained at sieve for both
10 and 20 minutes with diameter 53µm is the highest. Thus, it can be deduced
that lactose has larger particle size compared to MCC because for the particles
cannot pass a certain sieve is due to the particles are bigger than the
aperture of the sieve.
There are errors throughout the
experiment. The main error in the experiment is the loss in weight of lactose
powder and MCC after the experiment compared to their weight before the
experiment. The weight of both lactose and MCC are 100g initially. However,
after the experiment, the weight of lactose powder is found to be 98.4796g for
10 minutes and 97.8126 for 20 minutes. The weight of MCC is found to be 648716g
for 10 minutes and 73.4285g for 20 minutes.This may due to the lactose and MCC
powder are not completely removed after the sieving process. Some powders may
have been blown away during the vibration of sieve shaker, some of them may
have sticked to the sieve nest, some may have spilt out from the sieve nest
when we were transferring the powders from the sieve to weighing boat to be
weighed. Some of the powders may have been contaminated with other powders as
this experiment is carried out using both lactose and MCC.
To minimise the error, a few
precautions have to be taken. First, the sieves have to be tightly closed when
the sieve shaker is operating. The sieves should be cleaned thoroughly before
repeating the experiment with another type of powders to prevent contamination.
Besides, after the sieving process, the powders have to be removed from the
sieve nest to the weighing boat slowly and carefully to prevent the spillage of
the powders, causing inaccuracy in the weight of powders in each sieves.
CONCLUSION:
In this experiment, the
objectives of the experiment are achieved. The particle size distribution of
powder and the size of solid particle of lactose and microcrystalline cellulose
(MCC) by sieve nest successfully determined. The most particles size of lactose
after sieving for 10 minutes are in the range of bigger than 500µm (7109801%)
while for 20 minutes are in range of 300-500µm (4701352). While for sieving of
MCC for 10 minutes, most particles size are in the range of 53 – 150µm
(50.6871%) while for 20 minutes are in range of 53 - 150µm (44.4114). Hence
from the experiment, MCC has smaller particle size than lactose.
REFERENCES:
Martin,A.N. 2006.
Physical Pharmacy: Physical Chemistry Principles in Pharmaceutical Sciences.
5th Edition. Philadelphia: Lea & Febiger.
Jillavenkatesa A,
Dapkunas S J, Lin-Sien Lum, Particle Size Characterization, NIST Special
Publication , 2001
Patrick J. Sinko,
Yashveer Singh. 2011. Martins Physical Pharmacy and Pharmaceutical Pharmacy
Sciences. Ed. ke6. China: Lippincott Williams & Wilkins.
