Title:
Evaluation on the effect of
different composition of tragacanth on the characteristics of a
suspension.
Objective:
To study the effect of the
composition of tragacanth on the texture, clarity and the colour of
the suspension, the rate of
sedimentation and viscosity of the suspensions of different
compositions.
Introduction:
Suspension
is a formulation where insoluble solid is suspended in a liquid when the
disperse phase is solid and the continuous phase is liquid. Suspension not only
available in oral suspension, but also available in topical formulation. There
are many advantages to formulate drugs in suspension. For
example, some drugs are chemically unstable in solution but are stable when
suspended. Furthermore, some drugs have a bad taste when in solution but are
palatable when administered as undissolved particles. A good suspension must be
homogenously dispersed when shaked, pourable, pleasant taste and texture and
also uniform particle size. Besides, they should also be ease of redispersion
of settled solid particles, prevent the formation of hard cake, physically and chemically
stable and resistant against microbial contamination.
Many active ingredients are insoluble in aqueous solution
and thus wetting agents should be added to wet the particles first in order to
suspend the solid in the aqueous phase. They act by reducing 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 good suspension will have a slow sedimentation rate and this
can be done by adding the suspending agent and increasing the viscosity of the
suspending medium. The ideal suspending agent should be viscous without shear
but less viscous when shaking to allow it to be poured out.
The sedimentation rate, viscosity, and physical
appearance of the suspension is being studied by observing, using the
viscometer and centrifuge.
Material:
Chalk, tragacanth, concentrated peppermint water,
syrup BP, double strength chloroform water,
and distilled water.
Figure 1: chloroform water
Figure 2: chalk
Apparatus:
Weighing boat, mortar and pestle, 50mL measuring
cylinder, 200mL measuring cylinder,
centrifuge tube, 100mL beaker
Procedure:
1.
Prepare a suspension formulation of Paediatric
Chalk Mixture by using the following formula:
Chalk 3g
Tragacanth refer
to the table below
Concentrated peppermint water 0.6mL
Syrup BP 15mL
Double strength chloform water 75mL
Distilled water, q.s. 150mL
|
Paediatric 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
|
Figure 3: Syrup BP is added into suspension
2.
Pour 5 mL of the suspension into a weighing
boat and observe the texture, clarity and colour of the suspension formed.
3.
Pour 50 mL of the suspension into a 50mL
measuring cylinder and measure the height of the solid phase that is sedimented
at intervals of 5 minutes for 1 hour.
Figure 4: the suspension is stirred as precaution step
4.
Pour the remaining suspension (95mL) into a
100mL beaker and determine the viscosity by using the viscometer.
5.
Pour 10mL of the suspension
into a centrifuge tube and determine the height of the solid phase after
centrifuging at 1000rpm for 5 minutes at 25°C.
Results and Discussions:
1) Compare the physical
appearance of the suspensions formed. Explain.
Figure 5: Four different suspensions
There are 4 difference quantity of
tragacanth used in this experiment. For group 1 and 5, there are no tragacanth
used, whereas group 2 and 6 are using
0.1g of tragacanth. For group 3 and 7, 0.3g of tragacanth used and lastly for
group 4 and 8, 0.5g of tragacanth used in their suspensions formulation.
As compared, for
suspension where there are no tragacanth used, the colour of suspension formed
are white, the texture are a bit watery, and for the clarity, we could see
there are two separated layer formed where one layer is white and the other one
is a bit clear. Once we shake the suspension, it will form a cloudy suspension
and when no shear is given, the suspension rapidly separated into two layers.
As for the suspension
with 0.1g of tragacanth, the suspension formed are, less viscous and easily
sediment and redisperse, with an opaque appearance, and the colour of
suspension are milky white
For the suspension with
0.3g tragacanth, it is a bit same with the suspension containing 0.1g of
tragacanth. It is just a bit more viscous but still easy to pour and the rate
of sedimentation not too slow.
For the last
suspension, with 0.5g of tragacanth, the suspension formed is a bit viscous and
showing an opaque appearance, and the colour of suspension are milky white. The
rate of sedimentation is the slowest compared to other suspension. The
viscosity also is the highest.
In this experiment, we are using
tragacanth as the suspending agent, Tragacanth solution is viscous in nature,
it provides thixotrophy to the solution. The maximum viscosity of the solution
of Tragacanth is achieved after several days, because several days to hydrate
completely.
2) Plot a graph of height against time. Explain.
Figure 6: Suspension at t=0
Figure 7: suspensions has settled down
Figure 8: Graph of sediment height against time (tragacanth=0g)
There is no
tragacanth added in the suspension. Tragacanth plays a role in suspending the
solid ingredient in suspension. Thus it takes a short period of time for
sedimentation. At t= 0, no sedimentation occurred. At the first five minutes,
the suspension starts to sediment at the bottom of the measuring cylinder at
4cm height. It continues to settle rapidly. The sedmentation is complete at
t=25 minutes.
3)Plot a graph of sediment heights against time for
the suspension formulations which contain different amount of Tragacanth. Give
explanation.
|
Time
(min)
|
Sediment
heights (mm)
|
|||||||||||||
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
||
|
Amount of
Tragacanth (g)
|
0.0
|
0.0
|
4.0
|
3.0
|
2.5
|
2.5
|
2.0
|
2.0
|
2.0
|
2.0
|
2.0
|
2.0
|
2.0
|
2.0
|
|
0.1
|
0.0
|
0.0
|
3.0
|
3.0
|
3.5
|
3.5
|
4.0
|
4.0
|
4.5
|
4.5
|
4.5
|
5.0
|
5.0
|
|
|
0.3
|
121.0
|
121.0
|
120.0
|
119.0
|
119.0
|
119.0
|
118.0
|
118.0
|
118.0
|
117.0
|
117.0
|
117.0
|
117.0
|
|
|
0.5
|
120.0
|
120.0
|
118.0
|
117.0
|
117.0
|
117.0
|
117.0
|
117.0
|
116.0
|
116.0
|
116.0
|
115.0
|
115.0
|
|
Average
sediment heights (mm) (x±SD):
|
Amount of
tragacanth (g)
|
x±SD
|
|
0.0
|
2.154±0.875
|
|
0.1
|
3.385±0.989
|
|
0.3
|
118.5±1.45
|
|
0.5
|
117±1.581
|
Figure 9: Graph of sediment height against time (tragacanth=0.1g)
Figure 10: Graph of sediment height against time (tragacanth=0.3g)
Figure 11: Graph of sediment height against time (tragacanth=0.5g)
The
experiment is set up with tragacanth with three different amount. Tragacanth is
a suspending agent. It is used to increase the suspending capacity of the
insoluble compound and make it viscous. The higher the amount of tragacanth,
the lower the rate of sedimentation. But if the amount is too high, it will
cause difficulty to agitate the suspension because it is too viscous.
In
the first setup, there is no tragacanth added to the suspension. The result is
it takes less than 30 minutes, which is the shortest time for sedimentation of
the solid ingredient. This is because it is not able to suspend in the liquid
suspension.
For
the other three setup, tragacanth is added but with different amount. The
suspension with tragacanth added 0.5g takes the longest time to settle
completely on the bottom. The high amount of tragacanth allows the suspension
to suspend for a long time. This is important for drugs because the patient
might not taking the active ingredient which will sediment if no suspending
agent is added, thus causing less therapeutic effect.
An error occurs which the suspension
with 0.1g tragacanth sediment completely at the same time with the suspension
with 0.5g tragacanth. Therefore,
precaution steps must be taken to avoid inaccuracy of the results. First, the
suspension must be stirred or agitated before taking the readings of the
sediment height. Next, the eye level must be perpendicular with the scale on
measuring cylinder when taking the value.
4) Briefly
explain on mechanism analysis of viscometer. Plot a graft of viscosity against
the amount of tragacanth. Explain.
Figure 12: The viscosity of the suspension is measured with viscometer
Group
1
|
Reading
|
1
|
2
|
3
|
4
|
5
|
6
|
|
Viscosity (cP)
|
0.5
|
0
|
0.5
|
0.5
|
1.0
|
0.5
|
|
Average + SD
|
0.5+0.29
|
|||||
Group 2
|
Reading
|
1
|
2
|
3
|
4
|
5
|
6
|
|
Viscosity (cP)
|
0.5
|
0.5
|
0.5
|
1.5
|
2.0
|
1.0
|
|
Average + SD
|
1+0.58
|
|||||
Group 3
|
Reading
|
1
|
2
|
3
|
4
|
5
|
6
|
|
Viscosity (cP)
|
1.5
|
1.5
|
1.5
|
1.5
|
1.5
|
1.5
|
|
Average + SD
|
1.5+0
|
|||||
Group 4
|
Reading
|
1
|
2
|
3
|
4
|
5
|
6
|
|
Viscosity (cP)
|
20
|
20
|
10
|
10
|
0
|
10
|
|
Average + SD
|
11.67+6.87
|
|||||
|
Tragacanth amount (g)
|
0.0
|
0.1
|
0.3
|
0.5
|
|
Viscosity (cP)
 |
0.5+0.29
|
1+0.58
|
1.5+0
|
11.67+6.87
|
Figure 13: Graph of viscosity against the amount of tragacanth
The
viscosity of the suspension in this experiment is measured by using the
viscometer. There are different amount of tragacanth added to determine the
influence of the amount of tragacanth on the viscosity. The tragacanth act as
suspending agent which helps the suspending medium to support the insoluble
solid and thus decrease the rate of sedimentation.
Based
on the graph, the viscosity increased
proportionally to the amount of the tagacanth. The absence of tragacanth cause
the insoluble solid settle down rapidly. The tragacanth will reduce the
sedimentation rate of the insoluble solid. The more the tragacanth added will
have more effect on the sedimentation rate. But the type of tragacanth should
be considered as they may be charged particles and may affect the suspension.
Suitable tragacanth should be chosen. The ideal suspending agent will viscous
without shear and less viscous when shaking.
The aim to support the insoluble
solid in the suspending medium for a longer time is to prevent it from forming
hard cake that is difficult to be redispersed. This may cause inaccurate dosing
which can be overdose or underdose. By having a good suspension which is
readily to be redispersed, the accurate dose most probably can be achieved.
Flocculation is the way to prevent formation of hard cake.
There are some errors that occur
during this 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. The divided suspension contains uneven
distributed insoluble solid especially for the suspension without tragacanth
which settle down very rapidly.
Care must be taken during the use of
the viscometer. The viscometer used in the experiment in the lab is the falling
piston viscometer. This viscometer works based on the piston and cylinder
assembly. The piston is raised by an air lifting mechanism, drawing the
material being measured down through the clearance between the piston and the
wall of the cylinder into the space which is formed below the piston as it is
raised.
5) Plot a graph of
ratio of height of sediment as a result of centrifugation vs weight of
tragacanth. Give explanation.
|
|
Height (mm)
|
|
Before centrifugation
|
80
|
|
After centrifugation
|
17
|
|
Height Ratio
|
17/80 = 0.213
|
|
|
Height (mm)
|
|||
|
Group
|
1
|
2
|
3
|
4
|
|
Before centrifugation
|
80
|
80
|
80
|
80
|
|
After centrifugation
|
17
|
11
|
18
|
19
|
|
Height Ratio
|
0.213
|
0.138
|
0.225
|
0.238
|
Average: 0.2035
Standard deviation: 0.0448
|
Weight of Tragacanth (g)
|
0.0
|
0.1
|
0.3
|
0.5
|
|
Ratio of height ( x ±SD)
|
0.213 ± 0.0448
|
0.138 ± 0.0448
|
0.225 ± 0.0448
|
0.238 ± 0.0448
|
Figure 14: Graph of ratio of height of sediment against weight of tragacanth
A
hyperbola graph should be obtained. However, what we have here is a graph which
is nearly of hyperbolic-shaped. There might be some inaccuracy occur when the
experiment is being carried out. For example is inaccuracy in measurement.
Height of sediment decreases slowly with an increase in weight of tragacanth.
The higher the content of tragacanth, the lower the height of sediment formed.
This is because suspensions which contain more tragacanth is more stable.
Formation of sediment is not encouraged in an ideal suspension. In addition,
sedimentation can be prevented or minimized by controlled flocculation. In an
ideal suspension, the particles are flocculated, which are weakly bonded,
settle rapidly, do not form cakes(sediment) and easily resuspended. Besides, an
ideal suspension has high viscosity at negligible shear (storage) and low
viscosity at high shear (shaking, pouring, spreading).
6)
What is the function for each of the ingredients used to prepare these
suspensions? How the usage of different
amount of the tragacanth affect the physical characteristic and stability of a
suspension formulation.
The formulation for the Pediatric Chalk
Mixture :
|
Chalk (CaCO3)
|
3 g
|
|
Tragacanth
|
0.0g,0.1g,0.3g,0.5g respectively for
each suspension
|
|
Concentrated Cinnamon Water
|
0.6 mL
|
|
Syrup BP
|
15 mL
|
|
Double Strength Chloroform Water
|
75 mL
|
|
Distilled Water, q.s.
|
To 150mL
|
Chalk(calcium carbonate) is the active
pharmaceutical ingredient for this formulation, it used as antacid and
indigestion remedy, and also to treat diarrhoea, particularly in children. Tragacanth act as
suspending agent, where most suspending agents perform two functions. Besides
acting as a suspending agent they also add viscosity to the solution.
Suspending agents will form a film around the particle and decrease attraction
between the particle(cohesion forces). It also act as thickening agents. They
increase in viscosity of the solution, which is necessary to prevent
sedimentation of the suspended particles as per Stoke’s’s law. A good
suspension should have well developed thixotropy, where it have low viscosity
when high shear is applied, and have high viscosity when left at rest(no
shear). The determination of amount of suspending agent is depend whether there
are any other suspending agents presence, or the availability of other
ingredients that may act as suspending agent or contributes to the viscosity of
the suspension. Concentrated cinnamon water is acting as a flavouring agent, it
is the last ingredient to be added to making up to volume because it is a
volatile ingredient. But in our experiment, we are using the peppermint oil as
a substituent for the cinnamon water as it is not available at that time. Syrup
BP contains 66.7% w/w of sucrose as the solute in 33.3% w/w of water as the
solvent. It may also act as a thickeners due to its viscosity, and also as a
flavouring agent due to its sucrose contents.
Double Strength Chloroform Water is as
a preservatives, the amount is high because in this formulation contain a
preferable environment for microbial growth. Lastly is the distilled water as
the vehicle to make up the volume until 150 mL.
The
physical stability of suspension was mainly dependent on the type of suspending
agent rather than the physical characteristics of the drug. Thus, the amount of
the suspending agent used must not be too low nor too high. The calculation need to be done first to determine the amount
the suspending agent needed. If the amount is too high, then the suspension
will be too viscous and harder to be poured. When the amount is too low, the
suspension will tend to sediment quickly and may affect the dose when taken.
Conclusions:
Tragacanth is an
important ingredient in suspension to thicken and increase the viscosity as
well as to increase suspending capacity of drugs. Suspension with tragacanth
appears viscous and cloudy. The suspension would not separate the insoluble ingredient
from the liquid phase. The suspension will settle slowly, but readily
redispersed upon shaking. The suspension also can be poured readily and evenly.
Different amount of tragacanth
produce different suspending capacity towards the dispersed phase. Higher
amount of tragacanth is preferable for suspension to decrease the sedimentation
rate. Other suspending agent also can be added into suspension such as bentoite
and xanthan gum.
References:
- Aulton,
M.E & Taylor, K
(eds.). 2007. Aulton's Pharmaceutics: The Design and Manufacture of
Medicines, 3rd edition. Edinburgh: Churchill
Livingstone.
2. http://standard-deviation.appspot.com/
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