Experiment 2:
Effects of different composition of ingredients on the characteristics of
suspension formulation
Date of experiment: 31/3/15
Lecturer's name: Dr. Haliza Katas
Introduction
Suspension is a disperse system
whereby the insoluble solid ( dispersed phase) will dispersed in a liquid (
continuos phase).
An ideal suspension should has
different characteristic in the presence or absence of the shear. During shear
or when the force is applied, the suspension should possess the fluid
characteristic that the dispersed phase should be readily dispersed in the
continuous phase which facilitate the pouring of the suspension out from the
container with suitable opening. Meanwhile, during the absence of shear or the
suspension is at the storage condition, the suspension should possess the
viscous characteristics that the suspension will sediment in order to maintain
its stability . However, it is not until the stage of dispersed phase will coalesce
until it causes caking to occur. Upon shaking, the suspension should readily
dispersed. Good formulation of suspension will also not for, the bubbles or
foam.
Suspension formulation can be in a
few dosage forms, for examples, oral, topical and parental. The example for parenteral
suspension is the antibiotic powder that need to be reconstituted or dissolve
in suitable vehicles under the aseptic condition before injected into the body.
It is good to formulate certain drug
in suspension form as these drugs are insoluble in liquid and it is more stable
for the drugs to suspend in the liquid form rather than dissolving it.
Suspension will also solves the problem of bad taste as the suspension is
viscous and it will prevent the direct contact of the drug with taste
bud.Besides, it is good to prepare the drugs in suspension form as the choice
of the additives, for examples, colourants, preservatives, flavoring and others
are broader as the solubility of these additives in the formulation is not of
the concern besides the compatibility issue.
Various additives or excipients are
required in order to maintain solubility, stability and other properties of the
suspension. For examples, wetting agent, flavoring agent and coloring agent.
Wetting agent (eg: Tragacanth) will works in such a way that it will reduce the
surface tension between the dispersed phase and continuous phase and hence
prevent the dispersed phase from coalescing and caking. Suspension is
classified as coarse suspension where the particle diameter is more than 1 µm, or colloidal suspension where the
particle size is less than 1 µm. active ingredient. Hence, the composition of the ingredients in the suspension will
determine the characteristics of a suspension.
Objective
To determine the effects of
different amount of Tragacanth used to the formulation of a suspension.
Ingredients and apparatus
|
Apparatus
|
Ingredients
|
|
Weighing
instrument
|
Chalk
|
|
Weighing
boat
|
Tragacanth
|
|
Mortar
and pestle
|
Concentrated
Peppermint Water
|
|
200 ml
measurable cylinder
|
Syrup
BP
|
|
150 ml
plastic bottle
|
Double-strength
chloroform water
|
|
100 ml beaker
|
Distilled
water
|
|
50 ml
measurable cylinder
|
|
|
1 set
of 1 ml pipette and pipette bulb
|
|
|
1
centrifugator tube 15 ml
|
|
|
100
ml beaker
|
|
|
Coulter
counter instrument
|
|
|
Centrifugator
|
|
|
Viscometer
|
|
Procedures:
1.
One
formulation of Pediatric Chalk Mixture (150 ml) was prepared by the following
formulation.
|
Chalk
3g
|
|
Tragacanth
(referred to the Table 1)
|
|
Concentrated
Cinnamon Water 0.6 ml
|
|
Syrup
BP 15 ml
|
|
Double
Strength Chloroform Water 75 ml
|
|
Distilled
Water, q.s. 150 ml
|
Table 1
|
Pediatric
Chalk Mixture
|
Group
|
Tragacanth
(g)
|
|
I
|
1,5
|
0.0
|
|
II
|
2,6
|
0.1
|
|
III
|
3,7
|
0.3
|
|
IV
|
4,8
|
0.5
|
2. 5 ml of suspension was poured
into the weighing boat and labeled. Texture, clarity and color of the
suspension formed was described and compared.
3. 50 ml of suspension was poured
into 50 ml measurable cylinder. Height of the solid phase precipitated in the
cylinder was measured at the interval of 0, 5, 10, 15, 20, 25, 30, 40, 50 and
60 minutes.
4. The rest of the suspension (95
ml) was poured into 100 ml beaker and the viscosity of the suspension was
measured by a viscometer.
5. 10 ml of suspension was poured
into centrifugator tube and the height of the solid phase was measured after
centrifugation (1000rpm, 5 minutes, and 25°C).
Results and discussion
1.
Compare
the physical appearance of formed suspension and gives comments.
|
Suspension
|
Texture
|
Clarity
|
Colour
|
|
I
|
Very
dilute solution with less viscosity which enable sediment and redispersed
easily.
|
Less
turbidity or cloudy
|
Cloudy
|
|
II
|
Dilute
solution with less viscosity and easily dispersed.
|
Moderate
turbidity or cloudy
|
Light
milky white
|
|
III
|
Concentrated
solution with less viscosity and easily dispersed
|
Opaque
|
Milky
white
|
|
IV
|
Very
concentrated solution with more viscosity and difficult to disperse
|
Opaque
|
Milky
white
|
Varies amount of tragacanth used
will produce different appearance of suspension in turn of appearance and
clarity. Suspension labelled I,II,III and IV contain certain amount of
tragacanth as shown in table 1.
According to the result shown above,
the viscosity of the suspension can be compares as follow,
Suspension IV, Suspension III, Suspension II, Suspension I
Decreasing
order of viscosity
It is because suspension IV contains
larger amount of tragacanth.
Tragacanth plays an important role in maintaining the
stability of the suspension. There are two major roles of tragacanth in
suspension. Firstly, tragacanth will acts as a suspending agent.A suspending
agent helps to reduce the sedimentation rate of particles in suspension by
suspending the insoluble solid ( dispersed phase) within the liquid ( continuos
phase). Hence, the dispersed phase will remain stable in suspending within the
continuos phase and cloudiness is produced since the dispersed phase is not
soluble in the continuos phase.
Then, tragacanth also acts as a a
thickening agent that it will enables the water to diffuse into it and exert a
hydrostatic pressure, the higher hydrostatic pressure will causes it to swell
to gelatinous mass which give viscosity to suspension. Tragacanth that is
partly soluble in water also produce a viscous suspension.Hence, the suspension
I is a very dilute solution with less viscosity due yo the low tragacanth added
while the suspension IV has the greatest viscosity as it has the highest
concentration of tragacanth added.
2. Plot a graph of height of
sediment vs. times. Give explanation.
|
Time
( min)
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
|
Height
(mm)
|
0
|
0
|
2
|
2
|
4
|
6
|
9
|
10
|
10
|
10
|
10
|
10
|
10
|
The graph above has shown the height
of sedimentation of a suspension, Pediatric Chalk mixture which formulate with
0.3 g of tragacanth over one hour. According to the graph, the height of the
sediment formed at 10th minutes is low
which is 3 mm only and it remains until 15th minutes
After that, the height of the sediment will
increase for 20 minutes until it reaches the maximum height of 10 mm at 35th
minutes. Then, the maximum height of 10mm will remain.
At the beginning of the experiment,
the height of the sediment is 0mm which indicate that the suspension does not contain sediment.
When the time increases, sedimentation will occur. It is because more of the
insoluble solid molecules ( dispersed phase) will have the stronger cohesive
force among the dispersed phase which enable to flocculate. The larger the
flocculated dispersed phase, the higher is the rate of sedimentation as it
increases the diameter, according to Stoke's Law that as shown below.
V is the rate of sedimentation
D is the diameter
ρ is the difference of density
η is the viscosity.
The higher
the diameter, the rate of sedimentation will be greatly increased. Hence, when
the time goes, more sedimentation will occur that will increase the height of
the sedimentation will increase.
The
tragacanth that used in the experiment will aid to suspend the insoluble solid
particle in the liquid. The higher the amount of tragacanth added, the slower
is the rate of sedimentation. 0.3 g of the tragacanth that added into the
suspension will cause the insoluble dispersed phase to disperse in the
continuos phase for 5 minutes.
3. Plot a graph of height of sedimentation
against time for the formulation of suspension with different content of
tragacanth. Discuss.
|
|
Height (mm)
|
|
|
|
|
Time
( mins)
|
0.00
g of tragacanth
|
0.10
g of tragacanth
|
0.30
g of tragacanth
|
0.50
g of tragacanth
|
|
0
|
0
|
0
|
0
|
0
|
|
5
|
8
|
7
|
0
|
0
|
|
10
|
8
|
7
|
2
|
0
|
|
15
|
12
|
7
|
2
|
0
|
|
20
|
12
|
8
|
4
|
4
|
|
25
|
11
|
8
|
6
|
4
|
|
30
|
11
|
8
|
9
|
7
|
|
35
|
10
|
8
|
10
|
13
|
|
40
|
10
|
9
|
10
|
15
|
|
45
|
9
|
9
|
10
|
17
|
|
50
|
9
|
9
|
10
|
20
|
|
55
|
9
|
9
|
10
|
20
|
|
60
|
9
|
9
|
10
|
20
|
For the
first suspension which is without tragacanth,there is a large increase from 0mm
to 8mm during the first 5 minutes. This is because of the absence of
tragacanth. This will then increase the surface area between the dispersed
phase and as well as the Gibbs energy which cause the dispersed phases to be
thermodynamic come in close contact to each others and flocculate. Then, the
height of sedimentation will increase until 12 mm until 20th minutes which will
then gradually decrease and reach the equilibrium height of 9mm after 45th
minutes . The decreasing in the height of the sedimentation is due to the
present of the compact cake as more of the empty space is filled. The cake
formed which is denser will sink to the bottoms of the measuring cylinder. The
constant height of sedimentation of 9mm is achieved as all the empty spaces are
fully filled.
For the
second suspension with 0.10 g of tragacanth, the height of the sedimentation
will increase for the first 15 minutes to reach the maximum height of 9mm which
will then decrease until to 6mm for the remaining time. The height of the
suspension will increase as more sedimentation occurs. Starting from 40th
minute and onward, the height of the sediment reaches the maximum and remain
constant. This is because of the sediment will become more compact or the
dispersed phase will tend to coalesce and form cake at the bottom of cylinder
as the empty space between the dispersed phase will be filled with the
particles.
For the
third suspension with 0.3 g of tragacanth, the height of the sediment will
increases until 35th minute
and onward, the height remains constant. At
10th minute, only the height of the sediment will increases which is slower
than the suspension two that the height already increases for 7mm at 5th
minutes as the concentration of tragacanth used in suspension three is higher
than that of suspension two that make it becomes more stable and less favaroble
to sediment. Starting from 35th minute and onward,the height of the sediment
will remain constant due to the same reasons as mention above.
For the forth suspension with 0.5g
of tragacanth, starting from 20th minutes, only the sedimentation will
formed as the high amount of tragacanth
will prevent the formation of sedimentation. However, the height of sedimentation
will increase gradually to 20mm during the 50th minutes then the height of
sedimentation remain constant. Due to the high amount of tragacanth added, the
probability for the occurrence of sedimentation and as well as caking is very
low and hence the dispersed phase can dispersed uniformly within the continuous
phase.
4. Explain
briefly the mechanism of viscometer analysis. Plot a graph of the viscosity of
the suspension versus the amount of tragacanth (g). Give explanation.
The
viscometer is an instrument that used to measure the viscosity of the fluid. It
will works in such a way that it's motor will rotate on specific speed which
can be adjusted by the central controller. The spring will move the disc which
in turn rotate the stirrer at certain degree. The higher the rotation degree,
the higher is the rate of the rotation per minute and hence the this indicate
the more viscous the fluid is. The motor rotates a disc which enable the light
emitted from the Light Emitting Diode (LED) to fall on a photo-diode thus
undergoing amplification and this signal is then transmitted to a moving-coil
meter as a deflection.
|
|
Viscosity
reading (cP)
|
|
|
|
|
|
|
|
|
Tragacanth
|
1
|
2
|
3
|
4
|
5
|
6
|
Tragacanth
content (g)
|
Viscosity
(x±
SD)
|
|
I
|
0
|
0.5
|
1.0
|
1.0
|
2.0
|
2.0
|
0.0
|
1.08± 0.7362
|
|
II
|
2.8
|
2.9
|
2.3
|
2.5
|
2.5
|
2.7
|
0.1
|
2.62±0.1547
|
|
III
|
3.0
|
2.5
|
3.0
|
2.8
|
2.8
|
2.5
|
0.3
|
2.77± 0.1542
|
|
IV
|
1.0
|
3.0
|
4.0
|
4.0
|
4.5
|
4.5
|
0.5
|
3.50±1.22
|
Calculation on the viscosity
Suspension I
Average =0+0.5+1+1+2+2
6
= 1.08
SD=√ 10.25 -(1.08)²
6
=± 0.7362
Suspension II
Average= 2.8+2.9+2.3+ 2.5+ 2.5+
2.7
6
=2.62
SD=√ 41.33 -(2.62)²
6
=± 0.1547
Suspension III
Average= 3.0+2.5+3.0+2.8+2.8+2.5
6
= 2.77
SD=√46.18 - ( 2.77)²
6
= ±0.1542
Suspension IV
Average =1+3+4+4+4.5+4.5
6
=3.5
SD=√ 82.5. - (3.5)²
6
=±1.22
By theory, the viscosity of the suspension should be directly proportional to the amount of the tragacanth powder in the suspension since less sedimentation will occurs.The graph obtained should be linear where the viscosity of suspension is directly proportional to the amount of tragacanth. Suspending agents will increase the viscosity of the suspension, which is necessary to prevent sedimentation of the suspended particles.
From
this experiment, chalk is suspended by tragacanth (suspending agent) in the liquid
phase and form suspension. From the graph above, the increasing adding of tragacanth ,the higher
is the viscosity of suspension.
Increasing the weight of tragacanth, the gel-like structure formed will be
stronger and thus the suspension formed will be more viscous.
However, due to the occurrence of the errors, a straight line that pass
through the center of origin cannot obtain. This may due to the amount of
tragacanth added to suspension is not high enough. Therefore, the viscosity
graph of the suspensions obtained is different from theoretical graph.
5.
Plot a graph of the height ratio vs the amount of Tragacanth used in the
suspension. Give comments.
|
Weight
of tragacanth (g)
|
Before
centrifuge (mm)
|
After
centrifuge (mm)
|
Height
ratio
|
|
0.0
|
60
|
15
|
60:15/4:1
|
|
0.1
|
75
|
15
|
75:15/5:1
|
|
0.3
|
70
|
10
|
70:10/7:1
|
|
0.5
|
70
|
20
|
70:20/3.5:1
|
Based on the graph above, the increasing amount of tragacanth will increase the height ratio until it reaches the maximum height ratio of 7 when 0.3g of tragacanth is added , then the height ratio will decrease.
By theory, the more the amount of
tragacanth used, the lower should be the height ratio as the suspension is more
viscous and less sticky. This is also because of the more difficult is the
formation of sedimentation.
However, due to the errors occur in
the experiment, the result is not as expected.
6. What is the functions of every
ingredients that are used in the preparation of this suspension. How does the
use of tragacanth ingredients affect the physical and stability of a
suspension.
|
Ingredients
|
Functions
|
|
Chalk
|
Acting
as an active ingredient.
Therapeutic
function: absorbent that treat diarrhea.
Experimental
function:Make the suspension.
|
|
Tragacanth
|
Suspending
agent that will reduce the rate of sedimentation.
Thickening
agent that will increase the viscosity of the suspension.
|
|
Syrup
BP
|
Acting
as a sweetening agent and increase the viscosity of the suspension.
|
|
Concentrated
Peppermint water
|
Acting
as a flavoring agent that will mask the taste of the drug and improve
palatability of the preparation.
|
|
Double
strength chloroform water
|
Acting
as a preservatives that can lengthen the shelf life of the suspension.
|
|
Distilled
water
|
Diluent
in the suspension that will increase the volume of suspension to a desired volume.
|
Conclusion
When the amount of the tragacanth
increases, the rate of sedimentation will decrease and hence the height of the
sedimentation will decrease as well.
Reference
1. Pharmaceutics: the science of
dosage form design, Aulton, M.E.2002
2. British Pharmaceutical Codex 1973
