Objective
• To
investigate the effect of Tragacanth in suspension formulary.
Introduction
Suspension is a preparation containing finely
divided, insoluble drug particles uniformly distributed throughout a vehicle.
The disperse system is solid why continuous system is liquid. The disperse phase must be suspended evenly
in continuous phase in order for constant dosage delivery. Thus, in order to
increase the suspending capacity and slow down sedimentation rates, suspending
agents added to the formulation. Ideal
suspending agents shall have high viscosity at negligible shear (storage) and
low viscosity at high shear (upon shaking, pouring, spreading)
For this experiment, the suspending agent is
Tragacanth Powder, a natural dried gummy exudate that will forms viscous liquid
or gel when combined with water depending on concentration. Tragacanth is used
to suspend heavy insoluble. This
compound has to be used in the right amount for suspending disperse phase in a
suspension formulation.
APPARATUS
- Electronic
balance
- 1 weighing bot
- 1 set mortar
& pestel
- 150 ml plastic
bottle
- 50 & 200 ml
measuring cylinder
- 1 ml pipet &
pipet bulb
- 15 ml centrifuge
tube
- 100 ml beaker
- Coulter counter
- Centrifuge
- Viscometer
MATERIAL
- Chalk
- Tragacanth
- Concentrated
peppermint water
- Syrup BP
- Double-strength
Choloform Water
- Distilled water
PROCEDURE
|
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
|
Table
1
2.
The suspension was poured (5
ml) into weighing boat and was labelled. Observe and compare the texture,
clarity, and colour of the suspension.
3.
50 ml of suspension was poured
into 50 ml measuring cylinder, and every intervals of 0, 5, 10, 15, 20, 25, 30,
35, 40, 45, 50, 55 and 60 minutes; the height of suspended solid phase was
measured.
4.
The remaining (95 ml) of the
suspension was poured into 100 ml beaker and the suspension viscosity is
measured using viscometer.
5.
10 ml of suspension was poured
into a centrifuge tube and the height of solid phase was determined after
centrifugation (1000 rpm, 5 minutes, 25 ᴼC).
Results
Pediatric Chalk Mixture
|
I
|
II
|
III
|
IV
|
Tragacanth (g)
|
0.0
|
0.1
|
0.3
|
0.5
|
Texture
|
More diluted
|
Diluted
|
Concentrate
|
More concentrate
|
Clarity
|
Clear when still, cloudy when shaken
|
Clear when still, clear when shaken
|
Cloudy
|
More cloudy
|
Color
|
White
|
White
|
Milky white
|
Milky white
|
Tragacanth acts
as suspending agent by facilitating the dispersing of insoluble solid particles
in liquid medium, hence preventing their caking. In mixture I and mixture II
which have no and only 0.1g tragacanth respectively, they are diluted, clear
and white in colour. In the absence of tragacanth, chalks and other insoluble
solid particles sediment at the base, leaving the aqueous liquid phase above
them. They only redispersed upon shaking. In the increasing of tragacanth
added, we can see the texture becomes more concentrated and the clarity becomes
more cloudy, hence it means more insoluble solids dispersed in the liquid
phase.
Pediatric Mixture I
TIME
(min)
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
HEIGHT
(mm)
|
6
|
5
|
5
|
5
|
5
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
4
|
Pediatric Mixture I
Reading
|
1
|
2
|
3
|
4
|
5
|
6
|
Viscosity
|
2.50
|
3.00
|
4.50
|
2.50
|
3.30
|
4.10
|
Average + Standard Deviation
|
3.32±0.83
|
|||||
Pediatric Mixture I
Amount of Tragacanth (g)
|
0.0
|
0.1
|
0.3
|
0.5
|
Before centrifuge (mm)
|
27
|
8
|
80
|
74
|
After centrifuge (mm)
|
12
|
6.7
|
65
|
18
|
Height ratio
|
0.444
|
0.838
|
0.813
|
0.243
|
Questions
- Compare the
physical characteristics of the suspensions formed and give explanation.
Pediatric Chalk Mixture
|
I
|
II
|
III
|
IV
|
Tragacanth (g)
|
0.0
|
0.1
|
0.3
|
0.5
|
Texture
|
More diluted
|
Diluted
|
Concentrate
|
More concentrate
|
Clarity
|
Clear when still, cloudy when shaken
|
Clear when still, clear when shaken
|
Cloudy
|
More cloudy
|
Color
|
White
|
White
|
Milky white
|
Milky white
|
Tragacanth acts
as suspending agent by facilitating the dispersing of insoluble solid particles
in liquid medium, hence preventing their caking. In mixture I and mixture II
which have no and only 0.1g tragacanth respectively, they are diluted, clear
and white in colour. In the absence of tragacanth, chalks and other insoluble
solid particles sediment at the base, leaving the aqueous liquid phase above
them. They only redispersed upon shaking. In the increasing of tragacanth
added, we can see the texture becomes more concentrated and the clarity becomes
more cloudy, hence it means more insoluble solids dispersed in the liquid
phase.
2. Plot a graph of height of sendimentation
against time. Give explaination.
This experiment, during the beginning (0 min), the height of sediment suspension is 0.6 cm, this is due to the amount of tragacanth (suspending agent) is zero. Thus, the disperse phase is not suspended in continuous phase for a longer time as there are no suspending agents in the formulation. The height of sediment suspension gradually decreased and remains constant as it settled at the bottom of the flask and no longer suspended in the continuous phase.
- Plot a graph of height of sedimentation against time for the
formulations of suspension with different contents of Tragacanth. Discuss.
Time(min)
|
Average Sediment
Height (mm) (X±SD)
|
||||||||||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
|||
Tragacanth Content (g)
|
0.0
|
Group 1
|
0
|
2
|
5
|
5
|
6
|
6
|
7
|
7
|
7
|
8
|
8
|
8
|
8
|
Group 5
|
0
|
10
|
7
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
||
Average
|
0
|
6
|
6
|
5.5
|
6
|
6
|
6.5
|
6.5
|
6.5
|
7
|
7
|
7
|
7
|
||
0.1
|
Group 2
|
0
|
10
|
7
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
6
|
|
Group 6
|
11.8
|
11.6
|
11.5
|
11.3
|
11.2
|
11.1
|
11.1
|
11
|
11
|
11
|
10.9
|
10.9
|
10.8
|
||
Average
|
5.9
|
10.8
|
9.25
|
8.65
|
8.6
|
8.55
|
8.55
|
8.55
|
8.5
|
8.5
|
8.45
|
8.45
|
8.4
|
||
0.3
|
Group 3
|
0
|
0
|
0
|
3
|
4
|
6
|
8
|
10
|
10
|
10
|
11
|
11
|
12
|
|
Group 7
|
13.1
|
14
|
11
|
9
|
9
|
9
|
9
|
9
|
9
|
8
|
8
|
8
|
8
|
||
Average
|
6.55
|
7
|
5.5
|
6
|
6.5
|
7.5
|
8.5
|
9.5
|
9.5
|
9
|
9.5
|
9.5
|
10
|
||
0.5
|
Group 4
|
12.3
|
12.1
|
12.1
|
12.1
|
11.9
|
11.9
|
11.7
|
11.7
|
11.7
|
11.7
|
11.7
|
11.5
|
11.5
|
|
Group 8
|
12.5
|
12.5
|
12.5
|
12.3
|
12.2
|
12.2
|
12.2
|
12.2
|
12.2
|
12.2
|
12.2
|
12.2
|
12.2
|
||
Average
|
12.4
|
12.3
|
12.3
|
12.2
|
12.05
|
12.05
|
11.95
|
11.95
|
11.95
|
11.95
|
11.95
|
11.85
|
11.85
|
||
For suspension 1 (without tragacanth), there is a
sharp increase from 0 to 5 minutes which is then increases gradually. The sharp
increase is due to the absence of tragacanth. Therefore, the content settles to
the bottom quickly. As time passing, the height of sediment should decreases
gradually. This is because the particles filled in the spaces between the
porous structures to make the sediment become more compact. The sediment forms
a cake at the bottom of the measuring cylinder. However there are some errors
that cause the readings are inaccurate.
For suspension 2 (with 0.1g of tragacanth), there is an
increase from 0 to 5 minutes which is then decreases gradually. However,
compared to suspension 1, the rate of sedimentation of suspension 2 is slower.
This is because of the presence of tragacanth makes the active ingredients
suspended in the suspension. As time passing, the height of the sediment
decreases gradually like in the suspension 1. This is also due to the filling
of spaces between the porous structures which in turn makes the sediment to
become more compact and forms cake at the bottom of the measuring cylinder.
For suspension 3(with 0.3g tragacanth), the height of
the sediment increases slowly and remains constant from 50 to 55 minutes. This
is due to the presence of tragacanth in the suspension which makes suspension 3
to become more stable. The greater the amount of suspending agent used, the
longer the time taken for the sediment to form. Suspending agents capable to
suspend the particles in the suspension which counteract the gravity force,
thus forming a more stable suspension and prevent caking from happens.
For suspension 4 (with 0.5g tragacanth), there is no
sediment observed from 0 to 20 minutes. The height of the sediment is then
remains constant from 30 to 50 minutes. With a high amount of tragacanth, the
particles remain suspend in the suspension which counteract the gravity force,
thus there is no caking of suspension. The suspension is said to be stable.
4. Explain the mechanism of viscometer
analysis. Plot a graph of viscosity of a suspension formulation against
tragacanth content. Give explanation.
Viscometer used in this experiment
is rotational viscometer that works by determining the required force for rotating
a disk or bob in a fluid at known speed. It uses a precision servo motor to
drive the shaft. The Spindle or rotor is attached directly to the shaft. High
speed microprocessors measure the speed from a digital encoder and calculate
the current required to drive the rotor at the test speed. The current required
is proportional to the viscosity of the sample under test.
Amount of
tragacanth(g)
|
Readings
|
Viscosity(cP)
|
Viscosity(cP)
(Average±SD)
|
0.0
|
1
|
7.40
|
8.733±1.124
|
2
|
9.40
|
||
3
|
7.70
|
||
4
|
9.50
|
||
5
|
8.20
|
||
6
|
10.20
|
||
0.1
|
1
|
7.00
|
6.583±0.801
|
2
|
6.50
|
||
3
|
6.00
|
||
4
|
6.00
|
||
5
|
6.00
|
||
6
|
8.00
|
||
0.3
|
1
|
3.00
|
4.900±0.1221
|
2
|
4.70
|
||
3
|
5.90
|
||
4
|
4.00
|
||
5
|
5.90
|
||
6
|
5.90
|
||
0.5
|
1
|
13.20
|
12.967±6.972
|
2
|
6.20
|
||
3
|
16.80
|
||
4
|
19.20
|
||
5
|
18.20
|
||
6
|
4.00
|
The viscosity decreases from 0.0g of tragacanth to 0.3g tragacanth
but increases rapidly from 0.3g to 0.5g of tragacanth. Errors have occurred in
the beginning because the viscosity is supposed to be increasing instead of
decreasing. Tragacanth acts as a suspending agent. Most suspending agents
perform two functions. Besides acting as a suspending agent they also imparts
viscosity to the solution. Suspending agents form film around particle and
decrease interparticle attraction. Suspending agents 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.
where
V is the sedimentation rate (cm/sec), d the diameter of the suspended particles
(cm), r1 its density and r2 is the density of the medium(g/cm3), g is the
acceleration of gravity (980.7 cm/sec2) and ho is the viscosity of the external phase in poises (g/cm sec).
Suspending or thickening agents
are added to suspensions to thicken the suspending medium, thereby reducing the
movement (sedimentation) of suspended particles and physically stabilizing the
product. This is particularly important in flocculated systems in which rapid
particle settling is the primary factor leading to physical instability and
lack of dosage uniformity in the product. As from Stoke’s Law, applying
flocculation as a means of preventing caking, can be done by increasing the
particle diameter, and thus increase the rate of sedimentation. A good
suspension should have well developed thixotropy. 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 the mouth of bottle. Thus, increasing amount of
suspending agent used increased the viscosity of suspension.
5. Plot a graph of sediment height ratio
after centrifugation versus the amount of Tragacanth (g). Give explanation.
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.
6. What is the functions of each ingredient use in
preparation of this suspension? How the use of different content of tragacant
will effect the physical and stability characteristics in the suspension?
Chalk is use as
the active ingredient of the suspension. It will provides the pharmacological
activity to affect the structure or any function of the body of man or animals.
Tragacanth is use as suspending agent which will keep the active ingredient to
suspend. Concentrated peppermint water and Syrup BP are use for flavouring agent which give good taste for
suspension. Double strength chloroform water is use as preservative to prevent
the product from being contaminated. Distilled water use for make up the volume
that need for the preparation. The amount of tragacanth use as suspending agent
is important in determine the viscosity of the suspension. If it is too much,
the suspension will be too viscous to agitate the suspension. If suspension
agent do not use will cause the substance to be suspended cannot be suspended
even in shorter time. Thus the stability can be increase by the increase
viscosity. But it has least physical activity because the sedimentation and
formation of caking.
Conclusion
The rate of
sedimentation and the height of sediment formed in the suspension depend on the
amount of different tragacanth powder used to form the suspension. The higher
the amount of tragacanth powder, the lower the height of sediment formed. This
is due to the action of tragacanth powder that prevents the solution from
sendimenting.
References:
1. Michael
E.Aulton, Aulton’s Pharmaceutics The Design And Manufacture of Medicines, third
edition, 2007, Churchill Livingstone Elsevier
2.
http://abacus.bates.edu/~ganderso/biology/resources/centrifugation.html
