TITLE
The use of wetting agent in Suspension
OBJECTIVE
To study the effect of different
amount of tragacanth on the sedimentation rates of suspensions.
INTRODUCTION
Suspension
is a heterogeneous system consisting at least two phases whereby a
finely-divided solid is dispersed in a liquid (dispersion medium). The
continuous or external phase is generally a liquid or a semi-solid. The
dispersed or internal phase is made up of particulate matter which is
essentially insoluble in, but dispersed throughout, the continuous phase. Suspensions
are intended for oral administration as sweetened, flavored formulations or for
topical application where they are referred to as ‘lotions’. They are also used
as non-sweetened, non-flavored formulations for many parenteral routes of
administration such as intraocular, intranasal, intravenous, and intramuscular.
Besides,
suspensions possess certain advantages over other dosage forms. Some drugs are
insoluble in all acceptable media and must, therefore, be administered as a
tablet, capsule or as a suspension. This is because some drugs are typically
stable in the form of suspension rather than in solution. One of the functions
of suspension is to mask the bad taste of some drug. Drugs in suspension are
chemically more stable than in solution. A good
suspension should be physically and chemically stable, resistant to microbial
contamination, homogenously dispersed when shaken, easily poured and consists of
uniformly dispersed size particles.
There
are some disadvantages of suspensions relative to other dosage forms. The
primary disadvantage is their physical instability. For example, they tend to
settle over time leading to a lack of uniformity of dose. This can be minimized
by careful formulation and by shaking the suspension before each dose is
delivered. Therefore, it is better to decrease the rate of settling and to
permit easy re-suspension of any settled particulate matter rather than trying
to eliminate the separation. One of the ways is to use the wetting agent such
as tragacanth to reduce the surface tension. Wetting agents which are also
known as surfactants have to be added because the drugs are not readily
suspended in the liquid medium.
MATERIALS AND METHODOLOGY
1 x 1ml graduated pipette 5
x100ml beaker
1 x pipette bulb Parafilm
1 x weighing boat 1 x weighing
balance
1 x set of mortar and pestle 1 x
Viscometer
1 x 50ml graduated cylinder 5 x
plastic bottle
5 x 250ml graduated cylinder
MATERIALS
Chalk Double
strength chloroform water
Tragacanth Distilled
water
Concentrated peppermint water Syrup BP
METHODOLOGY
1. A
suspension of Pediatric Chalk Mixture (150ml) is prepared according to the
following formula :
Ingredient
|
Suspension
|
|||
A
|
B
|
C
|
D
|
|
Chalk (g)
|
3
|
3
|
3
|
-
|
Tragacanth (g)
|
0.0
|
0.1
|
0.3
|
0.5
|
Concentrated peppermint water (mL)
|
0.6
|
0.6
|
0.6
|
0.6
|
Syrup BP (mL)
|
15
|
15
|
15
|
15
|
Double Strength Chloroform water (mL)
|
75
|
75
|
75
|
75
|
Distilled water q.s. (mL)
|
150
|
150
|
150
|
150
|
2. 5ml
of the suspension is poured into a weighing boat and labelled each formulation.
The texture, clarity and color of each suspension are observed and compared.
3.
The
sedimentation rate of each suspension is determined. The suspension is shook
vigorously making sure all of the particles are uniformly suspended, and the
time is noted. The boundary between the sediment and the supernatant is
observed and the time it takes for the boundary to pass each 10ml graduation
until the volume of sediment has reached 80ml is recorded.
4.
The
best way to observe the boundary is to view it directly in front of a light
source. You might try viewing it with sunlight from the windows as your light
source. You should note whether there is a clear and distinct boundary or no
obvious boundary.
5.
The
gradated cylinder is set down on the lab bench, and the lab timer started at
this point.
6. For
suspension A to D, the sedimentation volume of the suspension are recorded at t=0,2,5,10,15,30min.
7.
The
obtained data are recorded in the following table:
Suspension
|
Sedimentation volume at pre-determined time
(min)
|
Distinct boundary
(yes/no)
|
||||||
0
|
2
|
5
|
10
|
15
|
30
|
|||
A
|
||||||||
B
|
||||||||
C
|
||||||||
D
|
||||||||
8.
The
sedimentation volume ratio is calculated using the following formula:
Sedimentation volume ratio = Hu/Ho
Hu: ultimate
height of the sediment, ie. The height of the sediment at a particular time.
Ho: initial
height of the total suspension.
9. The
ease of re-dispersibility of each formulation are examined after the last
measurement.
To do this:
To do this:
i. The
paraffin is make sure is snug on the mouth of the graduated cylinder, and
re-enforce the seal with gloved hand.
ii. The
number of inversions it takes to completely re-disperse the drug are counted
iii. The
observations are recorded.
10. 95ml of
suspension is poured into a 100ml beaker and the viscosity of the suspension
solution are determined using the viscometer at 100rpm per 30seconds.
11. The data is
recorded in the following table:
Suspension
|
A
|
B
|
C
|
D
|
Viscosity (cP)
|
||||
Mean
|
||||
SD
|
12. Each suspension
is poured into a plastic bottle. After storing all the suspension for a period
of 4 days, the ease of redispersion in each system is determined and which
system is the most acceptable.
RESULTS
Suspension
|
Texture
|
Clarity
|
Colour
|
A
|
Very
dilute
Coarse
Less
viscous
|
Clear
|
Milky
white
|
B
|
Viscous
Smooth
|
Cloudy
|
Milky
white
|
C
|
Viscous
Concentrated
Very
smooth
|
Very
Cloudy
|
White
|
E
|
Very
viscous
|
Clear
|
Yellowish
|
Table 1
Time taken for the
boundary to pass each 10ml graduation (s)
|
|||
Suspension A
|
Suspension B
|
Suspension C
|
|
10ml
|
40
|
More than 15mins
|
More than 15mins
|
20ml
|
45
|
More than 15mins
|
More than 15mins
|
30ml
|
62
|
More than 15mins
|
More than 15mins
|
40ml
|
80
|
More than 15mins
|
More than 15mins
|
50ml
|
105
|
More than 15mins
|
More than 15mins
|
60ml
|
112
|
More than 15mins
|
More than 15mins
|
70ml
|
135
|
More than 15mins
|
More than 15mins
|
80ml
|
168
|
More than 15mins
|
More than 15mins
|
Table 2
Suspension
|
Sedimentation volume
at pre-determined time (min)
|
Distinct boundary
(YES/NO)
|
|||||
0
|
2
|
5
|
10
|
15
|
30
|
||
A
|
45
|
30
|
25
|
19
|
18
|
14
|
Yes
|
B
|
45
|
22
|
21
|
21
|
21
|
20
|
No
|
C
|
45
|
45
|
44
|
40
|
34
|
30
|
No
|
E
|
45
|
-
|
-
|
-
|
-
|
-
|
No
|
Note: there is
no drug in Suspension E- observations are only taken at time=0
Table 3
Suspension
|
Sedimentation
volume ratio at pre-determined time (min)
|
|||||
0
|
2
|
5
|
10
|
15
|
30
|
|
A
|
1
|
0.67
|
0.56
|
0.42
|
0.40
|
0.31
|
B
|
1
|
0.49
|
0.47
|
0.47
|
0.47
|
0.44
|
C
|
1
|
1
|
0.98
|
0.89
|
0.76
|
0.67
|
E
|
-
|
-
|
-
|
-
|
-
|
-
|
Table 4
Suspension
|
Number of inversion
needed to re-disperse the drug
|
A
|
1
|
B
|
2
|
C
|
3
|
E
|
0
|
Table 5
Viscosity of the
suspension using viscometer at 100 rpm for 30s:
Suspension
|
A
|
B
|
C
|
E
|
||||||||
Viscosity (cP)
|
2.00
|
1.90
|
2.53
|
2.76
|
3.12
|
1.74
|
3.48
|
2.52
|
2.40
|
4.08
|
3.84
|
4.62
|
Mean
|
2.14
|
2.54
|
2.80
|
4.18
|
||||||||
SD
|
0.28
|
0.58
|
0.48
|
0.33
|
||||||||
Table 6
Formula to calculate SD :
For Suspension A
= 0.28
For Suspension B
= 0.58
For Suspension C
= 0.48
For Suspension E
= 0.33
The ease of redispersion after four
days:
Suspension
|
Number of inversion
needed to re-disperse the drug
|
A
|
2
|
B
|
6
|
C
|
11
|
E
|
0
|
Table 7
Suspension B is the most acceptable
system because it has a lower rate of settling and permits easy re-suspension
of settled particulate matter.
DISCUSSION
1. For
suspension A with 0.0 g of tragacanth powder, the texture is coarse and less
viscous. The absence of the tragacanth as the suspending agent caused the
suspensions to sediment very fast and the particles separated into two distinct
boundaries and become less viscous . This makes the clarity of the suspensions
to be clearer and less cloudy due to separation of water from the insoluble
ingredients. The color is white at the bottom and colourless at the top of the
suspensions.
For
suspension B with 0.1 g tragacanth powder, we can see that the texture is quite
smooth with very little sediment at first and the suspension is more viscous
than suspension A. This may be by the presence of the suspending agent which
helps to prevent settlement of the suspended solids under gravity. The clarity
of this suspensions is opaque compared with the clear suspensions A because the
suspensions do not seem to separate into two separate layers and they mix
together .The color is white.
For
suspension C with 0.3g of tragacanth powder, the texture is very smooth and very
viscous compared to suspension B. This is because an increase in the tragacanth
powder helps to mix the excipients very well and prevent sedimentation to occur
at a fast rate. While the clarity is much more cloudy because the excipients
bind together and no sedimentation occurs. The color is white, same with
suspension B.
Lastly
for suspension E with 0.5g of tragacanth powder and without chalk, the texture
is very viscous and smooth in comparison with suspension A, B and C. The only
present of tragacanth powder which is a wetting agent and acts as thickening agent, because it will
swell in water to gelatinous mass which gives viscosity to suspension.
This sample is yellowish in colour due to absence of chalk and it is
transparent.
2.
Suspension
|
Sedimentation
volume ratio at pre-determined time (min)
|
|||||
0
|
2
|
5
|
10
|
15
|
30
|
|
A
|
1
|
0.67
|
0.56
|
0.42
|
0.40
|
0.31
|
B
|
1
|
0.49
|
0.47
|
0.47
|
0.47
|
0.44
|
C
|
1
|
1
|
0.98
|
0.89
|
0.76
|
0.67
|
E
|
-
|
-
|
-
|
-
|
-
|
-
|
Table 4
Graph 1
The
graph above shows the relationship between the sedimentation volume ratio with
time. Based on the result, as the amount of tragacanth increase, the
sedimentation volume ratio of sedimentation will decrease. This results follow
the theory because tragacanth as the suspending agent helps to reduce the
sedimentation rate of particles in suspension. It works by increasing the
viscosity of the liquid particle, and thereby slowing down settling of solid
particle as per Stoke’s law. Besides, Tragacanth also forms a film around
particle and decrease interparticle attraction. It produce a deflocculated
system in which the suspension can disperse for a longer time and increase the
efficiency of suspension administration.
In
suspension A (0.0g of tragacanth), it did not have any suspending agent in the
suspension so there was a drastic change of the sedimentation volume ratio. The
sedimentation rate of suspension A is the highest.
In
suspension B (0.1g of tragacanth), there was presence of suspending agent in
the suspension so there sedimentation rate is relatively slow compare to suspension
A.
In
suspension C (0.3g of tragacanth), the sedimentation rate is the slowest as the
suspension contains the greatest amount of tragacanth.
In
suspension E (0g of chalk), there is no sedimentation occurs. It set as a
control of the experiment.
3. A
viscometer reading indicate the viscosity of the fluid, it measures the torque for
instance the force required to rotate a spindle in a
fluid. All fluids have an internal friction between molecules, and this
measures how well it flows. Due to the internal friction, energy is required to
move the liquid and viscosity is the measure of the resistance to flow. The
spindle is driven by a synchronous motor through a calibrated spring and the
deflection of the spring is displayed by the viscometer. By changing speeds and
spindles, a variety of viscosity ranges can be measured.
The minimum range is
obtained by using the largest spindle at the highest level; the maximum range
by using the smallest spindle at the slowest speed. The higher the reading
of the viscometer, the higher the viscosity. The greater the amount of
tragacanth in the suspension, the higher the viscosity of the suspension.
Tragacanth act as a suspending agent or a thickener which aid the powder to
disperse throughout the continuous phase. Therefore, tragacanth will surround
the powder particles and make them more hydrophilic to water, when the powder
become more hydrophilic, it can mingle well with water and show the viscous
property. The more the powder interact with water, the higher the viscosity of
the suspension.
Suspension
|
A
|
B
|
C
|
E
|
Tragacanth content
(g)
|
0.0
|
0.1
|
0.3
|
0.5
|
Viscosity (cP)
|
2.14
|
2.54
|
2.80
|
4.18
|
Table 8
Suspending
agent works to stabilized between the two phases, continuous phase of syrup and
DSCW as well the dispersed chalk powder by increasing the viscosity. According
to the Stokes Law, the greater the dynamic viscosity, the smaller the terminal
settling velocity of the solid particles.
Hence, reduce the sedimentation rate. Besides, tragacanth also decreases the surface tension between the phases. Therefore, the higher the amount of tragacanth used in the suspension preparation, the lower sedimentation rate; the higher the viscosity of the suspension. This results are tally with our experiment results.
The
greater viscosity of the suspension formed due to the higher amount of
tragacanth used during the preparation.
4. After storing the suspension for a period of 4
days, suspension A can still re-dispersed very easily due to the absence of
tragacanth and the number of inversion is only 2. Suspension B with 0.1g
tragacanth powder can be re-dispersed moderately easy which the number of
inversion is 6.
Suspension C which can hardly re-dispersed in the vehicle due
to the highest amount of tragacanth. The number of inversion for suspension C
to re-disperse is the longest among all, which is 11.
Lastly for suspension E, zero inversion is
needed as there is no sedimentation due to absence of chalk. In brief, this is
affected by the ability of the system to form deflocculated or flocculated
particle. In flocculated system suspensions, the dispersed particles are held
together by weak van der Waals forces and settle faster but produces a porous
sedimentation which is easily re-dispersed. In deflocculated systems however,
the dispersed particles settle slowly but will lead to the formation of compact
sediment which is difficult to be.
High amount of tragacanth powder added into
suspension will tend to form a deflocculated system, because continuous phase
has been thicken and thus each particle of chalk hard to contact with each
other. Also, the sedimentation rate is decreased by this viscosity. The
suspension C is a deflocculated system and is the most viscous. Thus it is not
easily re-dispersed. Flocculated system tends to exist in suspension with no
tragacanth powder, which happened in suspension A which appears to be
redispersed quite easily.
5. Based on all observation, product B will be the
most acceptable. This is because the amount of tragacanth, 0.1g added able to
let the chalk dispersed evenly for enough period of time to be poured and
dispensed to the patients. Furthermore, it is not too viscous, the number of
inversion is 6. This indicates when the suspension is being shaken, it
will not take too long for the active ingredient to re-disperse compared to
product C. This will enable the patients to get the exact amount of active
ingredients inside the suspension as needed. Hence, it is most acceptable
product.
6. In the experiment, chalk acts as an active
ingredient to determine the sedimentation rate of suspension after the addition
of tragacanth. Meanwhile, tragacanth acts as a wetting agent, also known as
surfactant. It is added to the suspension in order for the solid to disperse
evenly for longer time in the suspension. This can improve the stability of the
active ingredient. Concentrated peppermint water is a flavouring agent to mask
the unpleasant taste of the drug. It is added to the suspension to increase the
palatability of the suspension. Syrup bp is added as a sweetening agent.
Double Strength Chloroform water acts as a preservative for the suspension and
distilled water act as a vehicle in the suspension.
CONCLUSION
To conclude, as the amount of Tragacanth
increase, the sedimentation volume ratio of sedimentation will decrease. This is due to the action of Tragacanth powder that
prevent the solution from forming sediment. Tragacanth
acts as suspending agent and affect the sedimentation rate of suspension.
Amount of Tragacanth also affects the sedimentation height and viscosity of
suspension.
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 re-dispersed easily. Sedimentation system also occur in the
suspension when there is no Tragacanth and with this, suspension with no
Tragacanth is less viscous.
REFERENCES
1. Aulton,
M.E & Taylor, K (eds.). 2013. Aulton's Pharmaceutics: The Design and
Manufacture of Medicines, 4th edition. Edinburgh: Churchill Livingstone.
2. Florence,
A.T & Atwood, D. 2011. Physicochemical Principles of Pharmacy. 5th edition.
London: Pharmaceutical Press.
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