EXPERIMENT
1
Title:
The
use of wetting agent in suspension.
Objective:
To
investigate the effect of different amount of tragacanth on the sedimentation
rates of suspensions.
Date of experiment:
22th
September 2016
Introduction:
The
term “suspension” refers to a two-phase system consisting of a finely divided
solid dispersed (suspended) in a liquid (the dispersing medium). Suspensions
are heterogeneous systems consisting of at least two phases. The continuous or
external phase is generally a liquid or a semi-solid,
and 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." Suspensions are also used as non-sweetened, non-flavored
formulations for many parenteral routes of administration (e.g., intraocular,
intranasal, IV, IM, ID, SC).
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. Moreover, drugs in suspension are chemically more stable
than in solution. However, suspensions also possess some disadvantages relative
to other dosage forms. The primary disadvantage is their physical instability;
i.e., that they tend to settle over time leading to a lack of uniformity of
dose. This can, however, be minimized by careful formulation and by shaking the
suspension before each dose is delivered. Therefore, the best strategy is not
to try to eliminate separation, but rather to decrease the rate of settling and
to permit easy re-suspension of any settled particulate matter. One of the
strategies is to use wetting agent like tragacanth to reduce surface tension
and thus allows it to spread more easily.
Apparatus:
1
mL graduated pipette, pipette bulb, weighing boat, one set of mortar and
pestle, 50 mL graduated cylinder, 200 mL graduated cylinder, 100 mL beaker,
parafilm®, weighing
balance, viscometer.
Materials:
Chalk,
tragacanth, concentrated peppermint water (or any syrup BP flavouring agent),
double strength chloroform water, distilled water.
Methodology:
1.
A suspension of Paediatric
Chalk Mixture (150 mL) was prepared according to the following formula :
Ingredient
|
Suspension
|
|||
A
|
B
|
C
|
E
|
|
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.
5 mL of the
suspension was poured into a weighing boat and each information was labelled. Each
suspension was observed and its texture, clarity, and colour was compared.
3.
The sedimentation
rate of each suspension was determined. The suspension was shaken vigorously to
make sure all the particles were uniformly suspended. The boundary between the
sediment and the supernatant was observed and the time taken for the boundary to
pass each 10 mL graduation until the volume of sediment has reached 80 mL was
recorded by using a lab timer.
4.
The sedimentation
volume of the suspensions was also recorded at t = 0, 2, 5, 20, 15 and 30
minutes for suspensions A to D.
5.
The obtained data
was recorded in Table 1.
6.
The
sedimentation volume ratio was calculated using the following formula:
Sedimentation volume ratio = Hu/Ho
Hu : ultimate height of the sediment, i.e., the height
of the sediment at particular time
Ho : initial
height of the total suspension
7.
The ease of
re-dispersibility of each formulation was examined after the last measurement
by done the following steps:
i. The Parafilm® must be snugged on the
mouth of the graduated cylinder and the seal was reinforced with your gloved
hand.
ii. The number of
inversions it takes to completely re-disperse the drug was counted.
iii. The observations
was recorded.
8.
95 mL of
suspension was poured into a 100 ml beaker and the viscosity of the suspension
was determined by using a viscometer at 100 rpm for 30 seconds.
9.
The data was
recorded in Table 2.
10. Each suspension was poured into a plastic bottle. The
ease of redispersion in each system was determined after storing all the
suspensions for a period of 4 days and thus, the system that is most acceptable
was also determined.
Discussion:
Results:
Suspension
|
Texture
|
Clarity
|
Colour
|
A
|
Less viscous
|
Clear on top
Sediment formed at the bottom
|
Milky white
|
B
|
Viscous
|
Cloudy
Opaque
|
Milky white
|
C
|
Viscous
|
Cloudy
|
White
|
E
|
Very viscous
|
Clear
|
Yellowish
|
Time taken for the boundary to pass each 10ml graduation (s)
|
|||
Suspension A
|
Suspension B
|
Suspension C
|
|
10ml
|
34
|
More than 15 mins
|
More than 15 mins
|
20ml
|
57
|
More than 15 mins
|
More than 15 mins
|
30ml
|
80
|
More than 15 mins
|
More than 15 mins
|
40ml
|
102
|
More than 15 mins
|
More than 15 mins
|
50ml
|
122
|
More than 15 mins
|
More than 15 mins
|
60ml
|
144
|
More than 15 mins
|
More than 15 mins
|
70ml
|
167
|
More than 15 mins
|
More than 15 mins
|
80ml
|
182
|
More than 15 mins
|
More than 15 mins
|
Suspensions
|
Sedimentation volume at predetermined
time (min)
|
Distinct boundary (Yes/No)
|
|||||
0
|
2
|
5
|
10
|
15
|
30
|
||
A
|
145
|
105
|
40
|
20
|
20
|
20
|
Yes
|
B
|
145
|
118
|
96
|
75
|
40
|
40
|
No
|
C
|
145
|
145
|
142
|
140
|
139
|
139
|
No
|
E
|
145
|
-
|
-
|
-
|
-
|
-
|
No
|
Note:
there is no drug in Suspension E-observations are only taken at time=0
Sedimentation
volume ratio = Hu/Ho
Hu:
ultimate height of the sediment, i.e., the height of the sediment at a
particular time
Ho:
initial height of the total suspension
Suspensions
|
Sedimentation volume ratio at pre-determined time (min)
|
|||||
0
|
2
|
5
|
10
|
15
|
30
|
|
A
|
1
|
0.72
|
0.28
|
0.14
|
0.14
|
0.14
|
B
|
1
|
0.81
|
0.66
|
0.52
|
0.28
|
0.28
|
C
|
1
|
1
|
0.98
|
0.97
|
0.96
|
0.96
|
E
|
-
|
-
|
-
|
-
|
-
|
-
|
Suspensions
|
Number of inversion needed to
re-disperse the drug
|
A
|
2
|
B
|
4
|
C
|
6
|
E
|
0
|
Formula
to calculate SD :
x =
mean
∑ X = sum of viscosity
n = number of reading recorded
Viscosity of the suspensions using viscometer at
100rpm for 30s:
Suspensions
|
A
|
B
|
C
|
E
|
||||||||
Viscosity (cP)
|
4.50
|
4.50
|
4.50
|
5.40
|
5.40
|
5.40
|
7.20
|
7.20
|
7.20
|
8.70
|
8.70
|
8.70
|
Mean
|
4.50
|
5.40
|
7.20
|
8.70
|
||||||||
SD
|
0
|
0
|
0
|
0
|
||||||||
The ease of
re-dispersion after four days:
Suspensions
|
Number of inversion needed to re-disperse the drug
|
A
|
5
|
B
|
3
|
C
|
7
|
E
|
2
|
Discussion:
1. Compare and discuss
physical appearance of all suspension produced.
Suspension
A, B and C contain 0.0g, 0.1g and 0.3g of Tragacanth respectively. Suspension C
is viscous, white in colour with opaque cloudy clarity and barely form any
sediment. Suspension B is also viscous, milky white in colour with cloudy
clarity but the rate of sedimentation is higher than suspension C. In contrast,
suspension A is less viscous, forms 2 layers in which clear on top and
formation of sediment at the bottom. . In suspension A, the rate of
sedimentation is the highest as a result of absence tragacanth. This indicates
the presence of higher amount of tragacanth, the slower the rate of sedimentation.
Meanwhile, suspension E is very viscous, yellowish in colour with clear clarity
and no formation sediment. This is due to the absence of chalk.
2. Plot Hu/Ho vs. time for each of the
suspension (Table 1). Discuss the findings.
Based on the Graph
Hu/Ho versus Time, we found that Suspension A has the highest rate of
sedimentation, followed by Suspension B and Suspension C. As the time increases, the sedimentation
volume ratio will be decreased. This graph clearly displays the relationship
between the time and the sedimentation volume ratio of the suspensions.
For Suspension A, there
is a significantly fallen of sedimentation volume ratio in the first 5 minutes.
According to the theory, suspending
agent excipient, tragacanth aids the active pharmaceutical ingredients staying
suspended in formulation and preventing from caking to reduce the sedimentation
rate of particles in suspension. Since Suspension A does not contain any
tragacanth, therefore two distinct boundaries formed between the continuous
phase and dispersed phase and at the fastest rate. The suspension becomes less
viscous and the clarity of the suspension is clearer and less cloudy compared
to other suspensions due to separation of water from the insoluble ingredients.
For Suspension B, the
sedimentation rate is lower than Suspension A as there is the presence of 0.1g
of tragacanth. Tragacanth acts as a suspending agent forms a film around dispersed
particles(chalk) and decrease interparticle attraction so that the chalk powder
remains in the continuous phase to form a stable suspension. It also produces a
deflocculated system in which the suspension can be dispersed for a longer
period of time and increase the efficacy of suspension administration. The
appearance of the suspension is cloudy and milky due to the well dispersed of
the chalk powder. Less flocs are slowly formed in the first 10 minutes compared
to Suspension A.
For suspension C, the amount
of tragacanth is 0.3g which is the highest contain pf tragacanth among the
suspensions. The rate of sedimentation is the slowest compared to Suspension A
and B. More time is needed for the sediment to settle down to the bottom of the
measuring cylinder as the stability of the suspension is strong enough due to
the tragacanth. Since the tragacanth also imparts the viscosity of the
suspension, it causes the suspension C to be very viscous and makes the
suspension even more milky and cloudy compared to Suspension C. Hence, we can
make a conclusion of the amount of suspending agent contained in the
suspensions, the longer the time taken for the sedimentation to occur.
3. Briefly explain the principle of analysis
using viscometer. Plot the viscosity vs tragacanth content (Table 2). Discuss the
findings.
A viscometer is an
instrument used to measure the viscosity and flow properties of a fluid. All
fluids have an internal friction between molecules and the amount of energy
required to move the fluid will be different. Hence, there will be a variety of
viscosity result for different fluids. A viscometer utilizes the principle of
rotational viscometry - the torque required to turn an object, for example a
spindle, in a liquid demonstrates the viscosity of the fluid. Torque is applied
through a calibrated spring to a disk or bob spindle immersed in test fluid and
the spring deflection measures the viscous drag of the fluid against the
spindle. By changing speedand spindles, a variety of viscosity ranges can be
measured. Different viscosity of a fluid can be obtained by changing the
velocity and type of spindles.
Based on the graph
above, it obviously shows that the amount of tragacanth contained in the
suspension increases, the viscosity of the suspension also increases.
Tragacanth is a suspending agent which is as known as a natural hydrocolloid
viscosity enhancer. Suspending agent, tragacanth acts as thickening agent which
they will increase in viscosity of the suspension, which is necessary to
prevent sedimentation of the suspended particles as per Stoke’s’s law. Besides,
the tragacanth affects the surface tension between the dispersed and continuous
phase which forms film around particle and decrease interparticle attraction. The
viscosity of the suspension affects the rate of sedimentation.
The rate of
sedimentation can be estimated by Stoke's equation:
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).
When the viscosity of
the suspension is lower, the time taken for the dispersed particles to settle
down to the bottom of the measuring cylinder will be decreased. Thus, the
higher the amount of tragacanth powder contained in suspension , the higher the
viscosity of the suspensions.
4. After storing the suspensions for a period of 4
days, determine the ease of redispersion of each.
A : 5 inversions are needed to
re-disperse the chalk.
B : 3 inversions are needed to
re-disperse the chalk.
C : 7 inversions are needed to
re-disperse the chalk.
E : 2 inversions are needed to
re-disperse the chalk.
5. Based on all the observations, which product
would be considered to be most acceptable? Explain.
Suspension
C is the most acceptable product because it has the highest amount of tragacanth
(0.3g) which has the best effect on the suspension stability as the suspending
agent and thickening agent in suspension formulation compared to Suspension A
(0 g) and B (0.1g). The stability and physical properties of suspension will be
affected by using different amount of tragacanth. The higher the amount of
tragacanth in a solution, the more viscous the liquid vehicle is. This slower
down the rate of sedimentation. For an ideal suspension, it should settle
slowly, be readily re-dispersed just by gentle shaking and the suspension
should pour readily and evenly from its container. The easy re-dispersion of
sedimented particles evenly in a suspension is important for the uniformity of
dose. That is why Suspension C is the most acceptable because it possess these characteristics.
The viscosity of suspension also should be maintained at the optimum range to
have good stability of suspension as too high viscosity isn’t desirable and it
causes difficulty in pouring and administration. Also, it may affect drug
absorption since they adsorb on the surface of particle and suppress the
dissolution rate.
6. Briefly explain the
function of each excipients used in the suspension formulation. Explain the influence
of tragacanth on the physical characteristics and stability of a suspension.
Chalk is the active ingredient in this
formulation of suspension. The function of chalk is as absorbent that absorb
excessive fluid in watery faeces and make it more solid. Syrup BP function as a sweetening
and flavoring agent to mask the taste of the
suspension and increase the palatability. Double strength Chloroform Water is used as preservative to
prevent microbial contamination and also serves as vehicle for the formulation.
Distilled water is used as a vehicle and bulking agent to add the volume up to
150 ml. Concentrated peppermint water is used as flavoring agent that gives the
preparation a nice scent. Tragacanth is used as the suspending and wetting
agent that will decrease interfacial tension between dispersed phase and
continuous phase. In this experiment, the dispersed phase is chalk while the
continuous phase is distilled water. Tragacanth also acts as a thickening agent
in the suspension to increase the viscosity of the liquid vehicle which slow
down the settling of solid particles. Thus, it reduces the sedimentation rate
of chalk in suspension. This will lead to even distribution of the dispersed
phase in the continuous phase. Tragacanth also helps to facilitate
redistribution of a suspension on shaking. Different amount of tragacanth use in the suspension causes the suspension to have
different texture, clarity and colour. The
more tragacanth used, the more viscous the suspension as tragacanth is a thickening agent. Higher amount of tragacanth used also causes the
suspension to appear more cloudy as tragacanth is a suspending agent which
causes the suspended solid to dispersed evenly in the suspension. Higher amount
of tragacanth also causes the colour of suspension to look more stable , as the
suspended solid takes longer time to form
sediment at the bottom when the tragacanth used in increasing amount.
Conclusion:
The different amount of
tragacanth powder used will affect the rate of sedimentation of
suspensions and the height of sediment formed in the suspensions. As the amount
of tragacanth powder used increases, sedimentation rate of suspensions will be
slower and thus sediment height formed in suspensions will be lower.
References:
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