Title: Impact assessment of different
ingredients on the characteristics of a suppository formulation.
Objective: To study the effect of using
different base composition on the physical characteristics of a suppository
formulation.
Introduction:
Suppository is a solid
formulation with various sizes and shape that is suitable for rectal
administration. A good suppository must melt down
after administration into the rectal and release the drug for localized or
systemic effect. The drug needs to be dispersed in a suitable suppository base.
A good baseshould not be toxic, does not produce irritation, does not react with
the drug, and easy to form into a suppository. Different base composition will
affect the rate and release limit of a drug from suppository.
In
this experiment, the effect of different base composition on the physical
characteristics of the formed suppositories and its effect on the release of
the drug from it are studied.
Apparatus:
|
Weighing machine
|
Water bath (37°C)
|
|
Spatula
|
1 dialysis bag (10 cm)
|
|
1 weighing boat
|
2 strand of thread
|
|
1 beaker 50 ml
|
1 glass rod
|
|
1 beaker 100 ml
|
1 set of pipet (5 ml) and pipet
bulb
|
|
1 measuring cylinder 5 ml
|
1 plastic cuvette
|
|
1 set suppository mould
|
Spectrophotometer UV
|
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1 hotplate
|
|
Materials:
Polyethylene glycol (PEG) 1000
Polyethylene glycol (PEG) 6000
Paracetamol
Procedure:
1.
The Paracetamol powder (1g) is weighed
and prepared.
2.
Paracetamol suppository (10g) is
prepared using the following formula:
|
Suppository
|
Group
|
Materials
(g)
|
Solution
of saturated stock Paracetamol (ml)
|
Total
(g)
|
|
|
PEG 1000
|
PEG 6000
|
||||
|
I
|
1,5
|
9
|
0
|
1
|
10
|
|
II
|
2,6
|
6
|
3
|
1
|
10
|
|
III
|
3,7
|
3
|
6
|
1
|
10
|
|
IV
|
4,8
|
0
|
9
|
1
|
10
|
3.
The suppository is prepared by using
suppository-mould. The shape, texture, and color of the suppository is
explained and compared.
4. One
suppository is inserted into the beaker that contains distilled water (10 ml,
37°C) and the time taken required to melt it down is determined.
5. One
suppository is inserted into the dialysis bag and it is ensured that both ends
of the bed are tightly tied. Then, the bag is inserted into the beaker (100 ml)
that contains distilled water (50 ml), which is preheated to 37°C.
6.
At 5 minutes interval, one aliquot
sample (3-4 ml) is pipette and the release of Paracetamol from the suppository
is determined by using UV-visible spectrometer. It is ensured that the distilled
water is stirred with glass rod before taking the sample.
Result and discussion
1)
Compare
physical shape of suppository
|
suppositories
|
substances (g)
|
Mass of
paracetamol powder (g)
|
Total (g)
|
|
|
PEG
1000
|
PEG
6000
|
|||
|
I.
|
9
|
0
|
1
|
10
|
|
II.
|
6
|
3
|
1
|
10
|
|
III.
|
3
|
6
|
1
|
10
|
|
IV.
|
0
|
9
|
1
|
10
|
|
Suppositories
|
I
|
II
|
III
|
IV
|
|
Colour
|
Even white
|
Whitish
|
Uneven white
|
Whitish
|
|
Hardness/softness
|
Hard
|
Hard
|
Hard
|
Hard
|
|
Stickiness
|
Most sticky
|
Sticky
|
Non sticky
|
Less sticky
|
|
Smoothness
|
Smooth
|
smooth
|
Smooth
|
smooth
|
From the
table above, we can see that ratio between PEG
1000 and PEG 6000 can determine the physical properties of suppositories. As
the composition of PEG 1000 is increase, the softness of the suppositories
formed is increase. The melting point of PEG 1000 is 37-40 °C. It will
melt when it is inserted into rectum, which is the human body temperature is
37.5 °C.
While PEG 6000 shows that its hardness and not easily sticky.
When increase the composition of PEG 6000, the hardness of suppositories
increase. The melting point for PEG 6000 is 60-63 °C that is not easily melt in
human body temperature. It shows decrease in smoothness and stickiness.
2. Plot
a graph of time taken needed to melt the suppositories against the volume of
PEG 6000 in formulation. Compare and discuss the result.
|
Volume of PEG
6000 (g)
|
0
|
3
|
6
|
9
|
|
Time (min)
|
Group 1 : 65
Group 5 : 58
|
Group 2 : 10
Group 6 : 65
|
Group 3 : 60
Group 7 : 43.15
|
Group 4: 74
Group 8 : 61
|
|
Average time
taken (min)
(x ± SD)
|
61.5±4.9497
|
37.5±38.8908
|
51.57±11.9147
|
67.5±9.1923
|
PEG is a water soluble base for
suppository. It is an inert, non-ionic and long-chain polymer. Different types
of PEG with different molecular weight give differences effect in solubility,
freezing point, melting point, surface tension and others.
Based
on graph above, we would like to investigate the relationship between the mass
of PEG 6000 in formulation and the time taken needed to melt the suppositories.
In theory, suppository with higher amount of PEG 6000 will take longer time to
melt in the body’s fluid. This is because larger amount of PEG 6000 in the
formulation requires larger amount of water to make the suppository soluble and
thus increase the time taken needed to melt the suppositories. However, the
result does not comply with the theory accurately.
It is
shown on graph above that, in formulation with no PEG 6000 in the formulation
has longer time taken to melt the suppositories. This might be due to some
error while doing the experiment. Different technique used by different groups
such as stirring also might affect the result which may increase the rate of
dissolution of the suppository. Furthermore, the suppositories formed by might
be fractured when the suppositories were removed from the moulds. This would cause
the reduction of suppository sizes and thus the time required to melt a
suppository will decrease.
3. Plot
a graph of UV absorption against time.
|
Time
(min)
|
UV
Absorption
|
||||||
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
|
|
UV absorption at
520nm
|
0.000
|
0.0012
|
0.0014
|
0.0011
|
0.0012
|
0.0011
|
0.0016
|
The aim of this experiment is to
measure the amount of drug that can be released from the suppository into the
blood circulation based on its amount of ingredients that made up of PEG 1000,
PEG 6000 and the drug solution (paracetamol). The dialysis beg represents the
phospholipids membrane and the solution in the beaker representing the blood
plasma. The suppository was inserted into the dialysis bag and was immersed in
37˚C of water in order to provide a body temperature. The value of UV
absorption shown in the graph above correspond to the amount of paracetamol
release from the suppository in the dialysis beg into the surrounding solution
in the beaker.
Based
on graph above, there is some fluctuation in the reading obtained and this
might due to some errors while doing this experiment. In theory, it should be
increase in the reading of UV absorption with increasing time. In the first
5minutes, the reading obtained was increase exponentially. This might be due to
great difference in concentration gradient between water in beaker and
suppository in dialysis bag. Therefore, paracetamol diffuses out quickly.
Some
errors would be, uneven heating of water bath which will lead to inconstant
drug release rate from the suppository. Besides that, the suppository we made
may not be homogenously formed. This may cause the brittleness of PEG
suppository or trapped air space in the suppository thus reducing the size and
altering the drug release rate of drug from suppository dosage form. In
addition to that, distilled water in which the dialysis bag is exposed to may
not be stirred evenly before it is taken to be tested inn spectrophotometer UV.
4. Plot
a graph of UV absorption against time for different suppositories with
different composition. Compare and discuss the findings and result.
|
Time
(min)
|
Average
UV absorption at 520nm
|
|||||||
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
||
|
Suppositories
|
I
|
0.0071
|
0.1007
|
0.1472
|
0.1074
|
0.1096
|
0.1186
|
0.1540
|
|
II
|
0.0010
|
0.0131
|
0.0225
|
0.0225
|
0.0230
|
0.0235
|
0.0260
|
|
|
III
|
0.0110
|
0.0180
|
0.0170
|
0.0085
|
0.0220
|
0.0130
|
0.0160
|
|
|
IV
|
0.0050
|
0.0100
|
0.0405
|
0.0180
|
0.0250
|
0.0240
|
0.0255
|
|
The composition
of each suppository is as follows:
|
Suppository
|
Ingredients
|
|
|
PEG 1000
|
PEG 6000
|
|
|
1
|
9
|
0
|
|
2
|
6
|
3
|
|
3
|
3
|
6
|
|
4
|
0
|
9
|
Theoretically the suppository
with the highest amount of PEG 6000 will have the slowest release rate due to
the stronger hydrogen bonds (intermolecular forces) formed with Paracetamol
which will hinder the release of Paracetamol.
Suppository I has the highest rate of release because of the lowest
proportion or amount of PEG 6000 in the formulation and it is shown in the
graph above. Higher concentration of PEG-6000 results in decrease of the
releasing rate of drug because of the high viscosity of the matrix channels.
However, it does not shown in the graph/ data obtained. Suppository 4 should
has the lowest releasing rate as it contain the highest portion of PEG
6000,thus it will take longer time to melt in the body’s fluid. This is because
larger amount of PEG 6000 in the formulation requires larger amount of water to
make the suppository soluble and thus increase the time taken needed to melt
the suppositories. According to the findings, the most ideal composition in
suppositories formulation is the Suppository 2.
Inaccuracy
in the data might be due to some errors while doing this experiment. One of the
errors would be the stirring factor. Some group might not stir the solution
first before the solution was taken by using pipette to measure the UV absorption.
This will result with uneven distribution of the drug in the solution in the
beaker. Next is considering the freezing factor. Some group had put their
suppositories inside the freezer to harden the suppositories. This difference
will lead to different rate of dissolution of the suppositories.
5) What is the
function of each of the ingredients used in this preparation of suppositories?
How does the different amount of PEG 1000 and PEG 6000 affects the physical
characteristics of a suppository formulation and its rate of the release of
drug?
In the formulation of
suppository, we used paracetamol which act as an active ingredient. Paracetamol
also contain analgesic and antipyretic properties. Whereby polyethylene glycol
is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depends on its molecular weight is a type
of polymer. Both PEG 1000 and PEG 6000 are water miscible bases.
The suppository is meant to be administered by rectal route.
Therefore, right combination ratios between both PEG will allow the drug melt t
body temperature, optimum release of drug, increase the drug absorption and its
bioavailability. PEG 6000 has higher molecular weight compared to PEG 1000.
Thus, it has high melting point.
More amount of PEG 6000 than PEG 1000 will form hard, brittle
and low ability to dissolve. This cause lower drug release since higher melting
point is needed. The opposite will happen if PEG 1000 amount is higher than PEG
6000. Thus, the ratio of PEG will determine the drug dosage form hardness and
drug release.
Conclusion
1.
The
UV absorption should be increasing as the time increases. However, graph above
shows fluctuation pattern. This may be due to several errors during the
experiment.
2. Different ratio of PEG 1000 and
PEG 6000 may influence the physical
characteristics and the rate of release of drug of the suppositories
formulation. The more the ratio of PEG 6000 relative to PEG 1000, the harder,
more brittle and lower the rate of release of drug of the suppositories. The
lowest rate of release drug was suppositories contain only PEG 6000 while the
highest rate went to the suppository containing only PEG 1000.
References
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