“Suspension” is
a type of formulation in pharmaceutical products. It is 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. Usually, the continuous phase or external phase is generally
a liquid or semi-solid while 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, flavoured formulations or for topical application where they are
called as “lotions”. Suspensions are also used as non-sweetened, non-flavoured
formulations for many parental routes of administration such as intraocular,
intranasal, intravascular, intramuscular and intradermal.
Suspensions have
certain advantages compared to other dosage forms. Some drugs are insoluble in
all acceptable media and must, therefore, must be administered as a tablet,
capsule or as a suspension. Moreover, drugs in suspension are chemically more
stable than in solution. But, suspensions also possess some cons relative to
other dosage form. The major disadvantage is their physical instability. As an
example, suspensions 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 such as tragacanth to reduce surface
tension.
Aim:
To explore the
effect of different amount of tragacanth on the sedimentation rate of
suspensions.
Apparatus:
1 mL graduated
pipette 100
mL beaker
Pipettle bulb Parafilm
Weighing boat Weighing
balance
Mortar and
pestle Viscometer
50mL graduated
cylinder 200
mL graduated cylinder
Materials:
Tragacanth Distilled
water
Concentrated
peppermint water Syrup
BP
Procedures:
1. A
suspension of Pediatric Chalk Mixture (150 mL) is prepared according to the
following formula
Ingredient
|
Suspension
|
|||||
A
|
B
|
C
|
D
|
E
|
||
Chalk (g)
|
3
|
3
|
3
|
3
|
-
|
|
Tragacanth (g)
|
0.0
|
0.1
|
0.3
|
0.5
|
0.5
|
|
Concentrated
peppermint water (mL)
|
0.6
|
0.6
|
0.6
|
0.6
|
0.6
|
|
Syrup BP (mL)
|
15
|
15
|
15
|
15
|
15
|
|
Double Strength
Chloroform water (mL)
|
75
|
75
|
75
|
75
|
75
|
|
Distilled water q.s.
(mL)
|
150
|
150
|
150
|
150
|
150
|
|
2. 5
mL of the suspension is poured into a weighing boat and each formulation is
labelled. The texture, clarity and colour of each suspension are observed and
compared.
3. The
sedimentation rate of each suspension is determined. The suspension is shaken
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 10 mL graduation
is recorded until the volume of sediment has reached 80 mL.
4. The
gradated cylinder is set down on the lab bench and the lab timer is started at
this point.
5. For
suspensions A to D, the sedimentation volume of the suspensions at t= 0, 2, 5,
10 and 15 min is recorded.
6. The
sedimentation volume ratio is calculated using the following formula:
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
7. The
ease of re-dispersibility of each formulation is examined after the last
measurement.
8. The
parafilm is snug on the mouth of the graduated cylinder and the seal is
re-enforced with gloved hand.
9. The
number of inversions it takes to completely re-disperse the drug is counted and
the observations are recorded.
10. 95
mL of suspension is poured into a 100 mL beaker and the viscosity of the
suspension is determined by using viscometer at 60 rpm for 2 min.
11. Each
suspension is poured into a plastic bottle. The ease of re-dispersion in each
system is determined after storing all the suspensions for a period of 4 days.
The most acceptable system is determined.
Observation:
Suspension
|
Tragacanth Used
|
|||
Texture
|
Clarity
|
Color
|
||
A
|
0.0
|
Less viscous
|
Clear on top. Sediment formed at the
bottom.
|
Transparent on top, white sediment
formed at the bottom.
|
C
|
0.3
|
Viscous
|
Opaque.
|
Cloudy.
|
D
|
0.5
|
More viscous
|
More opaque.
|
More cloudy than suspension C.
|
Results:
Sedimentation rate of each suspensions.
Suspension
|
Time taken for the boundary to pass
each 10mL
(s)
|
|||||||
10mL
|
20mL
|
30mL
|
40mL
|
50mL
|
60mL
|
70mL
|
80mL
|
|
A
|
67
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
C
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
D
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
For suspension A, the maximum sediment formed after 30 minutes is only 10mL.
For suspension C, the maximum sediment formed is only 0.2mL after 30 minutes. Tragacanth is present in suspension C, reducing sedimentation.
For suspension D, there is no sediment formed at the bottom of the suspension after 30 minutes of observation. This is due to the presence of wetting agent, tragacanth in the suspension. Wetting agent reduce the surface tension of water and make the drug more effective in dispersing in the suspension and at the same time reduce as well as present sedimentation.
Suspension
|
Sediment volume at pre-determined time
(min) (mL)
|
Distinct boundary (yes/no)
|
|||||
0
|
2
|
5
|
10
|
15
|
30
|
||
A
|
0
|
10
|
13.5
|
10
|
10
|
10
|
Yes
|
C
|
0
|
0
|
0
|
0
|
0.2
|
0.2
|
No
|
D
|
0
|
0
|
0
|
0
|
0
|
0
|
No
|
Table
1
The sediment volume of suspension A
decreased from 13.5mL to 10mL at the 10 minutes is because
compression occurs. The drug particles start to settle down at the bottom of
the suspension and are compressed under the weight of overlying solids, water
is squeezed out while the space gets smaller.
Calculate the sedimentation volume ratio.
For A:
0 min: 0
0 min: 0
2
min: 10/100 = 0.1
5
min: 13.5/100 = 0.135
10
min: 10/100 = 0.1
15
min: 10/100 = 0.1 30
min: 10/100 = 0.1
For C:
(0, 2, 5, 10) min: 0
(0, 2, 5, 10) min: 0
30
min: 0.2/100 = 0.002
For D:
(0,
2, 5, 10, 15, 30) min: 0
Suspension
|
No. of inversions taken to completely
re-disperse the drug
|
A
|
1
|
C
|
1
|
D
|
0
|
Determination of viscosity:
x = mean
∑ X = sum of viscosity
1. Compare
and discuss physical appearances of all the suspensions produced.
Based on the results, suspension A has least viscosity
while suspension D is the most viscous one, and viscosity of suspension C fall
in between both suspensions. In suspension A, there is not wetting agent,
tragacanth present in it, hence it behaves more like water and able to flow
freely. On the other hand, suspension D contains the highest amount of
tragacanth which causes the suspension D to be the most viscous as tragacanth
will increase the size of chalk particles hence causes the flow of molecules to
be harder.
In term of clarity and colour, suspension A shows
clear on top but sediments are formed at the bottom. Suspension C is opaque
while suspension D is more opaque and cloudy than C. Due to the absent of
tragacanth, the chalk particles tend to sediment quickly and left the top part
free from chalk particles. In suspension C, the present of tragacanth causes
the chalk particles to disperse throughout the suspension and prevent them from
sediment to bottom. Since suspension D containing the highest amount of
tragacanth, more chalk particles are dispersed throughout the suspension.
2.
Plot Hu/Ho vs time for each of the suspension. Discuss
the findings.
Based on the graph, suspension A which does not contain tragacanth shows
high sedimentation volume ratio. At the first 5 minutes, the sedimentation
height increases, however the value drops to 0.1 and then remain constant. At
the beginning, chalk particles sediment quickly as the suspension does not
contain tragacanth. Later as more and more chalk particles sediment, the particles
compressed each other and filled up the spaces in between, this causes the
sedimentation height to decrease. When all the chalk particles are settled
down, the sedimentation height remain constant.
Due to the present of tragacanth in suspension C, the
chalk particles are dispersed well throughout the suspension, but as time
passes, there is a small portion of chalk particles sediment at the bottom.
In suspension D, there is no chalk particles settled
down at the bottom although after 30 minutes, as the amount of tragacanth is
very high, the chalk particles are very well dispersed.
3. Briefly explain the
principle of analysis using viscometer. Plot the viscosity vs tragacanth
content. Discuss the findings.
Viscometer
is used to measure viscosity and the flow properties of fluids. Viscosity is
defined as a liquid’s resistance to flow or shear stress. The viscosity must be
measured when consider process conditions for materials that need to be piped or
pumped. Besides, viscosity will indirectly measure the other physical
properties like molecular weight and density, which both influence the flow
properties. Therefore, viscometer is a very useful device to monitor batch
consistency and quality control.
Tragacanth is a suspending agent which will help to
increase the viscosity of suspension in order to reduce the rate of
sedimentation, so that the suspension will be more physically stable. Therefore
from the graph above, we can observe that the viscosity of suspension increases
when the tragacanth content increases.
4. After storing the
suspensions for a period of 4 days, determine the ease of redispersion of each.
After storing the suspensions for 4 days, it is
found that suspension A is the easiest to redisperse among the 3 suspensions,
whereas suspension C is easier to redisperse compared to suspension D.
5. Based on all the
observations, which products would be considered to be most acceptable?
Explain.
By
comparing suspension A,C and D, suspension C is the most acceptable suspension
due to some reasons. It is because suspension A has no tragacanth powder at all
wherelse suspension C has tragacanth . Suspension A appear to be more watery
and had more sediments than suspension C . However, suspension D had higher viscocity
than suspension C. Even though it appear to be good suspension at the
beginning, but when sediments occur, suspension D will be cake and will have
difficulty to redisperse compare to suspension C. Hence, suspension C is the
most acceptable products.
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.
The excipients
found in the suspension are chalk, Tragacanth powder, Concentrated peppermint
water, Syrup BP, Double Strength Chloroform Water and Distilled water.
The chalk act as
an active ingredient in the suspension. It is usually used to treat diarrhea as
it adsorb excess fluid in the faeces.
The function of
Tragacanth powder is to increase the viscosity of the solution. It act as a
thickening and suspending agent. It is necessary to increase the viscosity of
the solution because it prevent sedimentation of particles in the suspension.
The function of
concentrated peppermint water is to act as flavouring in the suspension.
Syrup BP also
act as a flavouring agent.
The function of
double strength chloroform water as an preservative agent to reduce microbial
growth in the suspension.
Distilled water
act as solvent in the suspension.
As we know
Tragacanth powder act as suspending and thickening agent, it is used to ensure
that a stable and uniform solution is form whereby there are no two distinct
layers of ingredients present in the suspension. Hence, amount of tragancath
will determine the viscosity of solution. Different amount of tragacanth will
cause formation of suspension with different texture and appearance. When the
tragacanth is present in the solution, the solution looks more cloudy and
smooth. However, the amount of tragacanth in the suspension must be moderate.
The higher the amount of tragacanth, the lesser the sedimentation occur. If the
viscosity of suspension is too high, the pourability will be decrease or might
results in caking which will be inconvenient for the patient.
Conclusion:
Tragacanth
powder is a good suspending agent. Tragacanth powder helps to increase the
viscosity of solution and produce suspension with smooth texture. It is because
Tragacanth can produce a stable suspension. The higher the amount of Tragacanth
powder, the lower the height of sediment formed, However, the amount of
Tragacanth powder must be moderate in order to produce a pourable suspension
with smooth texture with less sediment because if the amount of tragacanth powder
is too low, it will sediments will be formed but if the amount of tragacanth
powder is too much, caking will be formed and the suspension will have more
difficulty to rediperse.
Reference:
Reference:
1. John F.
Marriott, Pharmaceutical Compounding And Dispensing, 2006, Pharmaceutical Press
Sdn Bhd
2. Roland,
G. Piel, L. Delattre, B. Evrard International Journal of Pharmaceutics 263
(2003)
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