1. Title: Evaluation of the
effect of different amount of material on the characteristic of a suspension
formulation
2. Objective: To study the effect
that was produced by using varied amount of Tragacanth on a suspension
formulation
3. Introduction:
The
suspension dosage form has long been used for poorly soluble active ingredients
for various therapeutic indications. Development of stable suspensions over the
shelf life of the drug product continues to be a challenge on many fronts. A
good understanding of the fundamentals of disperse systems is essential in the
development of a suitable pharmaceutical suspension. The development of a
suspension dosage form follows a very complicated path.
The selection of
the proper excipients (surfactants, viscosity imparting agents etc.) is
important. The particle size distribution in the finished drug product dosage
form is a critical parameter that significantly impacts the bioavailability and
pharmacokinetics of the product. Appropriate analytical methodologies and
instruments (chromatographs, viscometers, particle size analyzers, etc.) must
be utilized to properly characterize the suspension formulation.
4. Apparatus:
Weighing device,
1 weighing boat, 1 mortar and pestle set, 1 plastic bottle 150 mL, 1 measuring
cylinder 50 mL 1 measuring cylinder 200
mL 1 pipette 1 mL and pipette bulb, 1
centrifuge tube 15 mL, 1 beaker 100 mL, Coulter counter device, centrifuge
device, and viscometer device.
Materials:
Chalk,
Tragacanth, Concentrated Peppermint Water, Syrup BP, Double-strength Chloroform
water and Distilled water.
5.
Procedure
1)
A suspension formulation of Pediatric
Chalk Mixture (150 ml) is prepared using those formula :
Chalk
|
3 g
|
Tragacanth
|
Refer Table 1
|
Concentrated peppermint 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 that has been formed
is poured and labeled into the weighing boat. Discuss and compare the texture,
clarity and colour of suspension formed.
3) Then,
poured 50 ml of the suspension into 50 ml measuring cylinder and within 0, 5,
10, 15, 20, 25, 30, 40, 50 and 60 minutes, the height of the solid phase that
sediment into the measuring cylinder being measured.
4) The
balance from the suspension (95 ml) is poured into 100 ml beaker and the
viscosity of the suspension is determined using viscometer.
5)
10 ml of the suspension is poured into
centrifuge tube and the height of the solid phase is measured. (1000 rpm, 5
minutes, 25 °C).
6.
Results:
Height of solid phase that is deposited
in the cylinder :
Time
(min)
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
Height
of solid phase (mm)
|
1113
|
20
|
15
|
13
|
1111
|
10
|
10
|
10
|
9
|
9
|
9
|
9
|
9
|
Time
(min)
|
Average
height of precipitates (mm) (x ±SD)
|
|||||||||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
||
Amount
of Tragacanth (g)
|
0.0
|
113
|
20
|
15
|
13
|
11
|
10
|
10
|
10
|
9
|
9
|
9
|
9
|
9
|
0.1
|
88
|
85
|
84
|
83
|
81
|
80
|
79
|
78
|
78
|
78
|
78
|
78
|
78
|
|
0,3
|
120
|
119
|
118
|
117
|
117
|
117
|
116
|
116
|
116
|
116
|
116
|
116
|
116
|
|
0.5
|
120
|
118
|
118
|
118
|
117
|
117
|
117
|
117
|
117
|
117
|
117
|
116
|
116
|
|
Viscosity of the suspension :
Tragacanth used is 0.0g (our group)
Readings
|
1
|
2
|
3
|
4
|
5
|
6
|
Viscosity
|
0.50
|
0.50
|
0.70
|
0.50
|
0.00
|
0.50
|
Average + SD
|
0.45 + 0.21
|
|||||
When Tragacanth used is 0.1 g :
Readings
|
1
|
2
|
3
|
4
|
5
|
6
|
Viscosity
|
1.00
|
0.50
|
0.50
|
0.50
|
0.50
|
0.50
|
Average + SD
|
0.58 + 0.19
|
|||||
When the Tragacanth used is 0.3g
Readings
|
1
|
2
|
3
|
4
|
5
|
6
|
Viscosity
|
2.00
|
1.50
|
1.50
|
1.50
|
1.50
|
1.50
|
Average + SD
|
1.58 + 0.19
|
|||||
When the Tragacanth used is 0.5g
Readings
|
1
|
2
|
3
|
4
|
5
|
6
|
Viscosity
|
2.00
|
4.50
|
4.00
|
4.00
|
4.00
|
4.50
|
Average + SD
|
3.83 + 0.85
|
|||||
Viscosity of the suspension
Amount of Tragacanth (g)
|
0.0
|
0.1
|
0.3
|
0.5
|
Viscosity (cP) (x ±SD)
|
0.45±0.21
|
0.58±0.19
|
1.58±0.19
|
3.83±0.85
|
Amount
of Tragacanth (g)
|
Before
centrifuged
|
After
centrifuged
|
Ratio
of heights
|
0.0
|
75
|
15
|
5
|
0.1
|
80
|
10
|
8
|
0.3
|
80
|
20
|
4
|
0.5
|
80
|
4
|
4
|
Heights of solid phase after being
centrifuged
7.
Discussion:
1. Discuss and compare the physical
characteristics of the suspension.
For this experiment,
the suspension is prepared with or without tragacanth. Tragacanth acts as
suspending agent or viscosity enhancer. It will reduce the rate of sedimentation
by increasing the viscosity of the suspension. For group 1 and 5, there are no
Tragacanth being added into the suspension. So, the suspension will look more
watery, it will be easier to sediment and redisperse. The suspension also less
viscous, so it will be less cloudy with two layers formed. The colour of the
suspension looks white and less milky compare to the others.
For group 2 and 6, only
0.1g of Tragacanth is being added into the suspension. The texture of the
suspension looks less viscous and easily redispersed. The colour of the
suspension looks milky white. While for group 3 and 7, 0.3g of Tragacanth is
added into the suspension. Compared to previous groups, this suspension looks
more viscous, but also easily redispersed. The appearance is more opaque and
the colour looks milkier. For the last group, group 4 and 8, 0.5g of tragacanth
is being added into the suspension. The suspension looks the most viscous and
the rate of sedimentation becomes more longer. The colour of the suspension
looks the milkiest compared to the suspension of other groups. It is also much
more difficult to redisperse.
2. Graph of
heights of sediment against time. Discuss.
The graph above
shows the relationship between the heights of sediment with time and the amount
of Tragacanth used. As observed on the graph, it is shows that the graph
rapidly decline with time. This is related to the amount of Tragacanth that was
used. For this suspension, the amount of Tragacanth used was 0.0 g. Tragacanth
acts as emulsifier, stabilizer, and thickening agent for the suspension.
Therefore, in the absence of Tragacanth, the suspension form sediment or layers
faster than suspension which contain Tragacanth.
3.
Plot a graph of height of sediment vs. time for the formulation of suspension
that contain varied amount of Tragacanth. Explain.
The graph above
shows the relationship between the heights of sediment against the time using a
different amount of Tragacanth. The
greater the amount of Tragacanth, the higher the height of sediment. This means
that the sediment is well dispersed in the system if the Tragacanth is
sufficiently provided. This shows the right characteristic of the suspension
which is well dispersed and does not form sediment faster after the suspension
is shaked. At 0 amount of Tragacanth which acts as surfactant, the sediment
form very faster. This shows that it is not suitable for characteristics of
suspension.
4.
Describe briefly the mechanism of viscometer. Plot a graph of viscosity vs.
weight of Tragacanth. Give explanation.
The mechanism of
viscometer analysis involved a motorized cylindrical rotor that is inserted
into a sample and rotated at constant speed using rotational viscometer. In
this experiment, the sample is placed in beaker. By using suitable metal
spindle, it is then rotated in the sample at fixed rpm, and the torque required
to rotate the spindle is measured. Based on the internal resistance to a
rotation provided by the shear stress of the sample, the sample’s absolute
viscosity can be determined. Absolute viscosity is in centipoise (cP),
equivalent to mPa.s in SI units.
The functions of
Tragacanth are as emulsifier, stabilizer and thickening agent. From the graph
above, we can see that the viscosity increase with increasing amount of
Tragacanth which 0.0 g of Tragacanth having 0.45 cP, 0.1 g having 0.58 cP, 0.3
g having 1.58 cP and 0.5 g having 3.83 cP. This is because Tragacanth, besides
acting as suspending agent, it also imparts viscosity to the solution.
Suspending agents form film around particle and decrease interparticle attraction.
Tragacanth increases the viscosity of the solution, which will prevent
sedimentation of the suspended particles.
A good
suspension should have well developed thixotropy. Thixotropy is the property of
certain gels of becoming fluid when shaken and then becoming semisolid again.
At rest the solution is sufficient viscous to prevent sedimentation and thus
aggregation or caking of the particles. When agitation is applied the viscosity
is reduced and provide good flow characteristic from mouth of the bottle.
Precaution
when measuring the viscosity is using the appropriate spindle of the viscometer
according to the amount of Tragacanth used so that correct results will be
achieved. Besides, the step in making the suspension also must be correct
because this will effect the value of the viscosity. Other than that, the weight
and amount of each material need to be weighed accurately because this also
will affect the results.
5.
Plot a graph of height of ratio of sediment as a result of centrifugation vs.
weight of Tragacanth. Give explanation.
Weight of Tragacanth
(g)
|
Before Centrifuge
(mm)
|
After Centrifuge
(mm)
|
Height Ratio
|
0.0
|
75
|
15
|
5
|
0.1
|
80
|
10
|
8
|
0.3
|
80
|
20
|
4
|
0.5
|
80
|
20
|
4
|
Gravity is mainly
associated with the slow sedimentation process of an immiscible mixture. A
common way to accelerate this sedimentation is by the use of centrifugation,
where the high achievable rotation frequencies permit an effective acceleration.
The graph showed the height ratio against weight of tragacanth. The amount of Tragacanth
used varied in the four formulations. Thus, result in different of height
ratio. The Tragacanth is used as a suspending agent where helps in reducing the
sedimentation rate of particle in suspension. It works by increasing the
viscosity of the liquid vehicle as to support the insoluble particle that are
dispersed in a liquid vehicle.
So, from the graph
above, it showed the height ratio is decreasing as the weight of Tragacanth
increasing. The stability will be measured from the height ratio. The least
height ratio will be the most stable suspension amongst others. Based on the
graph, suspension contained 0.3g and 0.4g is the most stable and theoretically,
suspension that has not contained any Tragacanth would be the least stable.
But, graph shows the 0.1 g Tragacanth has the highest height ratio, it might
due to some errors occur during the experiment. There are possibilities that
the Tragacanth used in the experiment has poor suspending agent properties as
compared to others.
6. What is the
function of each material that is used in the suspension formulation? How is
the use of different amount of Tragacanth affect the physical characteristic
and stability of a suspension formulation?
Chalk is an
adsorbent. It functions mainly through adsorption of toxin and other substances
that produce diarrhea. Tragacanth is a thickening agent. Tragacanth helps to
suspend chalk particles in the suspension, forming a flocculated system.
Tragacanth is chosen it has high viscosity at negligible shear and low
viscosity at high shear such as shaking, pouring, spreading. Double Strength
Chloroform Water is used as a preservative. It has a concentration of 50% as
suspension is prone to microbial contamination. Distilled water acts as a
vehicle. Concentrated Peppermint Water and Syrup are flavouring agents. Varied
amount of Tragacanth will affect the physical characteristic of the suspension,
whether the texture is rough or smooth. The stability of suspension that use
Tragacanth is good and but on prolonged storage is hard to redisperse.
Suspensions that do not use Tragacanth do not have good stability and the solid
particles inside will sediment rapidly but it is easily redisperse.
8. Conclusion:
Physical
characteristics and stability of a suspension are influenced by the varied
amount of Tragacanth. Suspension that does not contain Tragacanth has a rough
texture but it is easily redispersed. Sedimentation and deflocculated system
occur in the suspension when there is no Tragacanth. Suspension with no
Tragacanth is not viscous. Without Tragacanth, the sedimentation height due to
centrifugation is high as the suspension is not stable.
9. References:
1.
Aulton, M.E. 2002. Pharmaceutics: The
science of dosage form design. Edinburgh: Churchill Livingstone
2.
Banker, G.S. & Rhodes, C.T. 1990.
Modern pharmaceutics. 2nd Ed. New York: Marcel Dekker.
Florence, A.T. &
Attwood, D. 1998. Physico-chemical principles of pharmacy. 3rd Ed.
New York: Macmillan.
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