Experiment 2: Effects of different ingredients on the characteristics of
suspension formulation.
Objective: To know the effects of using different amount of tragacanth to the formulation
of suspension.
Introduction
Suspension is a heterogeneous mixture in which insoluble solid
is suspended in a liquid while the disperse phase is solid and the continuous
phase is liquid. There are certain types of suspension which are oral, topical,
parenteral and ophthalmic suspensions. Suspensions
can be advantageous compared to liquid dosage form in certain conditions. For
example, some drugs are chemically unstable in solution but are stable in
suspended condition. Moreover, some drugs may have unpleasant taste when in
solution form but are palatable when administered as undissolved particles. A
good suspension should have the following properties such as homogenously
dispersed when shaked, pleasant taste and texture, pourable and also uniform
particle size. Besides, they should have ease of redispersion of settled solid
particles, physically and chemically stable and resistant against microbial
contamination. Some of these characteristics are being evaluated in the experiment.
Since many active ingredients are
insoluble in aqueous solution thus wetting agents as well as surfactants have
to be added in order to suspend the solid in the aqueous phase. Among the
examples of wetting agents are tragacanth (will be used in this experiment) and
sodium lauryl sulphate. They will reduce the interfacial surface tension
between the drug particles and the suspension vehicles. Other excipients added
to a suspension are colouring agent, flavouring, syrup and preservatives. The
advantages of suspension are that it improves the stability of the active
ingredient, palatability and bioavailability of the formulation.
The sedimentation rate, viscosity,
and physical appearance of the suspension is evaluated with the viscometer and
centrifuge throughout the experiment.
Apparatus Ingredients
Weighing instrument Chalk
Weighing boat Tragacanth
Mortar and pestle Concentrated Peppermint
Water
150 ml plastic bottle Syrup BP
50 ml measurable cylinder Double-strength chloroform
water
200 ml measurable cylinder Distilled
water
1 set of 1 ml pipette and pipette bulb
1 centrifugator tube 15 ml
100 ml beaker
Coulter counter instrument
Centrifugator
Viscometer
Procedure
1.
1 formulation of Pediatric
Chalk Mixture (150 ml) was prepared by the following formulation:
Pediatric
Chalk Mixture
|
Group
|
Tragacanth
(g)
|
I
|
1,
5, 9
|
0.0
|
II
|
2,
6, 10
|
0.1
|
III
|
3,
7, 11
|
0.3
|
IV
|
4,
8,12
|
0.5
|
Chalk 3
g
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
2.
5 ml of suspension was poured
into the weighing boat and was labeled. Texture, clarity and color of the
suspension 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 duration 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. A little suspension
formed (5 mL) is poured into a weighing boat and labelled. The texture, clarity
and colour of the suspension formed is compared and explained
Pediatric
chalk mixture
|
Texture
|
Clarity
|
Colour
|
I
|
More dilute
|
Clear
|
Cloudy
|
II
|
Dilute
|
Not clear
|
Milky, chalky
|
III
|
Concentrated
|
Opaque
|
White
|
IV
|
More concentrated
|
Highly opaque
|
White
|
Mixture I do not contain
Tragacanth in their formulation. Therefore, the suspension is more watery and
less viscous but it is easy to sediment and redisperse. This is because no
suspending agent adsorbs on the particle surface provide low affinity to water,
hence it forms 2 layers providing a poor suspension. It is less cloudy due to
absence of Tragacanth. Formulation II, III and IV contain Tragacanth.
Therefore, the texture becomes smoother and more viscous when the weight of
tragacanth used increasing gradually. Suspending agent gives thicken and
provides ‘structure’ for the medium hence those formulations II, III and IV are
cloudy and give milky white colour. This
is because the suspension stays disperse in the medium for a longer time
compared to the formulation without Tragacanth. The opacity and the cloudiness
indicates that the disperse particles is totally dispersed in the medium. The amount of tragacanth must
not be too high because it will be too viscous to agitate and pour.
2.
The graph
above shows the relationship between the heights of sedimentation (mm) against
time (min). Based on the graph, as the time taken increases, the height of
sedimentation decreases. The suspension was white in colour. Some light are
used to observe the sedimentation clearly to avoid from making error. For the
last 5 minutes, the height of sedimentation of suspension has become no change
which is it maintain at 115 mm. This is because all of the Tragacanth in the
suspension has been sedimentated.
3.
Tragacanth is a supending agent
that will behave as protective colloids by coating the solid hydrophobic
particles with a multimolecular layer. This will impart hydrophilic character
to the solid and promote wetting. It promotes deflocculation by preventing
particles from getting held together easily.
In formulation I, the Tragacanth is
totally absent results in sedimentation of solid particles. From the graph, we
can see the height of sediment increases over time. This may be explained by
the DLVO theory. The electrical forces between the particles allow them to slip
past one another to form a closely packed arrangement at the bottom of the
container, with the small particles filling the voids between the larger ones.
Those particles lowermost in the sediment are gradually pressed together by the
weight of the ones above. The repulsive barrier is thus overcome, allowing the
particles to pack closely together. Physical bonding will lead to cake or clay
formation.
In formulation II, the height of sediment
formed is relatively low compared to formulation I. The height of sediment
decreases with increase of time due to 0.1g of tragacanth. When tragacanth is
used, a deflocculated system is formed. The dispersed particles remained as
discrete units. Settling will be slow because the rate of sedimentation depends
on the size of each unit. The slow rate of settling prevents the entrapment of
liquid within the sediment, which thus compacted and can be very difficult to
redisperse.
For formulation III,
the sediment increases with the increase of time. This is due to the inter–particular attractive
forces are stronger than the repulsive forces of the tragacanth powder on the chalk particles. Therefore,
the sedimentation formed increases with time.
For formulation IV, 0.5g of
tragacanth is used. The sediment decreases in height and remains constant after
20 minutes.
Viscometer is used to
measure viscosity. Viscometer will only work efficiently if the fluid has a
stable viscosity. It is important to ensure that either the fluid or the
viscometer to be in stationary when measuring the viscosity. The viscosity of
the suspension is said theoretically to be directly proportional to the amount
of Tragacanth used in the suspension. The viscosity of the suspension is an
important factor to control the rate of sedimentation of the suspension. When
the suspension has high viscosity, then it will take longer time to sediment
and settle.
4. Explain briefly the mechanism of
viscometer analysis. Plot a graph of viscosity of the suspension versus the
amount of tragacanth (g). Give explanation.
Amount
of tragacanth (g)
|
Readings
|
Viscosity
(cP)
|
Viscosity
(cP)
(Average±SD)
|
0.0
|
1
|
2.50
|
3.03±0.83
|
2
|
3.60
|
||
3
|
3.40
|
||
4
|
2.20
|
||
5
|
2.10
|
||
6
|
4.40
|
||
0.1
|
1
|
5.00
|
4.33±0.75
|
2
|
3.00
|
||
3
|
4.00
|
||
4
|
5.00
|
||
5
|
5.00
|
||
6
|
4.00
|
||
0.3
|
1
|
7.00
|
6.58±0.73
|
2
|
6.50
|
||
3
|
6.00
|
||
4
|
6.00
|
||
5
|
6.00
|
||
6
|
8.00
|
||
0.5
|
1
|
3.00
|
4.90±1.12
|
2
|
4.70
|
||
3
|
5.90
|
||
4
|
4.00
|
||
5
|
5.90
|
||
6
|
5.90
|
Amount of tragacanth (g)
|
0.0
|
0.1
|
0.3
|
0.5
|
Viscosity (cP)
(Average±SD)
|
3.03±0.83
|
4.33±0.75
|
6.58±0.73
|
4.90±1.12
|
Viscosity is an
internal property of fluid that offers resistance to flow or it is the measure
of the internal friction of a fluid. This friction becomes apparent when a
layer of fluid is made to move in relation to another layer. The greater the
friction, the greater the amount of force required to cause this movement which
is called shear. In this
experiment we used the sample of suspension as a simple case where the
shearing stress is directly proportional to the rate of shear. The
viscometer was designed and fabricate, it employs well known principle of
rotational spindle in the sample fluid.
They measure viscosity by sensing the torque required to rotate a
spindle at a constant speed while immersed in the sample fluid. The torque is
proportional to the viscous drag on the immersed spindle and thus to the
viscosity of the fluid. The motor is rotated at the speed of 300rpm which
is controlled by the central controller. Stirrer is rotated by disc which in
turn moved by spring more than 180°. Besides, the change of rotation degree is
directly proportional to the viscosity of the fluid and its rate of rotation.
Infra red radiations emitted by LED and diffuse through disc before detected by
photo diod. Change in degree of disc rotation will influence the infra red
radiation and this is detected and read by photo diod.
Based on the graph above, suspension with 0.3 g of tragacanth
shows the highest result in viscosity, but in theory the suspension with 0.5g
of tragacanth should give the highest reading of viscosity value, because the
viscosity is proportional to the mass of substances (tragacanth) and we should
get the linear plot of graph. The
more tragacanth added, the more viscous of the suspension being formed. Chalk
is suspended by tragacanth in the liquid phase and form suspension. But due to
some errors during the experiment, we could not get the same results as the
theory. The errors are this may be due to the insufficient amount of
tragacanth added to suspension. Besides that, viscometer may not be
appropriately cleaned from previous used. Therefore, the viscosity graph of the
suspensions obtained is different from theoretical graph.
6.
Plot
a graph of height of sedimentation formed after centrifuge against the
composition of tragacanth(g). Give your explainations.
Heights (mm)
|
|
Before spin
|
80
|
After spin
|
60
|
Height ratio
|
0.750
|
Height (mm)
|
|||||||||
Group
|
1
|
2
|
3
|
4
|
5
|
6
|
7
|
8
|
|
Before Spin
|
27
|
75
|
80
|
80
|
80
|
80
|
82
|
74
|
|
After Spin
|
12
|
10
|
74
|
60
|
10
|
67
|
21
|
18
|
|
Height Ratio
|
0.444
|
0.133
|
0.925
|
0.750
|
0.125
|
0.838
|
0.256
|
0.243
|
|
Average (0.0g) = Group 1 + Group 5
2
Average (0.1g) = Group 2 + Group 6
2
Average (0.3g) = Group 3 + Group 7
2
Average (0.5g) = Group 4 + Group 8
2
SD is calculated by using formula=
Tragacanth (g)
|
0.0
|
||
Group
|
1
|
5
|
x ± SD
|
Height Ratio
|
0.444
|
0.125
|
0.285±0.160
|
Tragacanth (g)
|
0.1
|
||
Group
|
2
|
6
|
x ± SD
|
Height Ratio
|
0.133
|
0.838
|
0.486 ± 0.353
|
Tragacanth (g)
|
0.3
|
||||||
Group
|
3
|
7
|
x ± SD
|
||||
Height Ratio
|
0.925
|
0.256
|
0.591 ±0.335
|
||||
Tragacanth (g)
|
0.5
|
||||||
Group
|
4
|
8
|
x ± SD
|
||||
Height ratio
|
0.750
|
0.243
|
0.497 ± 0.254
|
||||
Content of
Tragacanth(g)
|
0.0
|
0.1
|
0.3
|
0.5
|
Height Ratio( x ± SD )
|
0.285±0.160
|
0.492 ± 0.359
|
0.591 ±0.335
|
0.497 ± 0.254
|
Based
on the graph shown, the ratio of solid phase before centrifuge is increase due
to increases of mass of Tragacanth from 0.1g to 0.3g. When we did not insert tragacanth into suspension,
the ratio is 0.125:1. The height ratio of solid phase increases when tragacanth
was added into the suspension. This indicates that presence of tragacanth does affect
the solid phase in suspension. In theory, the higher the mass of tragacanth
presence, the higher the viscosity of suspension, the lower the rate of
sedimentation. Tragacanth solution is viscous in
nature and it provides thixotrophy to the solution. This enables it acts as a suspending
agent. Besides, tragacanth also imparts viscosity to the solution. Suspending
agents will form film around particles and decrease the interparticle attraction
so that adsorbed air is displaced from solid surfaces by liquid. This is required to prevent sedimentation of the
suspended particles as per Stoke’s’s law stated.
An ideal suspension should have well developed thixotropy. The solution should be viscous enough to prevent sedimentation and aggregation or caking of the particles at rest. The viscosity will be reduced and provides good flow characteristic from the mouth of bottle if agitation is applied. However, the result shown is inaccurate as the height ratio increases when the amount of tragacanth is increased as the height ratio is supposed to be decreased. This may due to the errors happened during the experiment. During the formulation of suspension, the weight of volume of the ingredients used may be measured inaccurately. The trituration of the suspending agent and the other ingredients may not be done well. During dividing the suspension, some of the insoluble solid had settle down and divided it without stirring it. Too much tragacanth added may causes the suspension to be too viscous and it is hard to determine the height ration after centrifuged.
An ideal suspension should have well developed thixotropy. The solution should be viscous enough to prevent sedimentation and aggregation or caking of the particles at rest. The viscosity will be reduced and provides good flow characteristic from the mouth of bottle if agitation is applied. However, the result shown is inaccurate as the height ratio increases when the amount of tragacanth is increased as the height ratio is supposed to be decreased. This may due to the errors happened during the experiment. During the formulation of suspension, the weight of volume of the ingredients used may be measured inaccurately. The trituration of the suspending agent and the other ingredients may not be done well. During dividing the suspension, some of the insoluble solid had settle down and divided it without stirring it. Too much tragacanth added may causes the suspension to be too viscous and it is hard to determine the height ration after centrifuged.
7. What is the role of each ingredients used in this suspension formulation? How does the amount of Tragacanth used can influence the physical characteristics and the stability of any suspension?
When a greater amount of Tragacanth
is added, the suspension becomes more viscous. As time goes by, the standing
suspensions will show the tendency to cake at the contact point at the bottom
of the container. Caking can be prevented so that the suspension can be
considered stable by adding Tragacanth or other suspending agent. Tragacanth
and other suspending agents work by enhancing the redistribution of a
suspension on shaking. This proves that with the increase in the amount of
Tragacanth, the sedimentation rate will reduce as sedimentation occurs in a
slower manner.
Conclusion
When the amount of tragacanth powder increases, sedimentation rate will be more slowly and thus sediment height will be lower.
References
1. Aulton, M.E.2002. Pharmaceutics: The Science of Dosage Form Design. Edinburgh: Churchill Livingstone.
2. British Pharmaceutical Codex 1973
3. http://www.tokisangyo.com/pdf/R85E.pdf
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