Objective: To study the effect of different composition of base
on the physical characteristic of suppositories.
Introduction:
Suppository is a solid formulation that has different
size and appearance and thus is suitable to be administered by rectal route. A
good suppository must be melt after being administered into the rectum and
release the drug content to achieve local or systemic effect. The drug must be
spread in a suitable base of suppository. A good base should be non-toxic, non-irritate,
no reaction with the drug and easily to be formed as a suppository. Different
composition of base will influence the rate and limit of drug release from the
suppository. In this experiment, the effects of the different base composition
to the suppository physical characteristics and also to the drug release
characteristics are evaluated.
Apparatus:
Weighing
instrument
Weighing
boat
Spatula,
Glass rod
100ml
beaker, 50ml beaker
Heater
(hotplate)
5ml
measuring cylinder
1
set of suppository mould
Dialysis
bag (10cm), Thread
Water-bath
(37°C)
1
set of pipette (5 ml) and pipette-bulb
1
plastic kuvet
Spectrophotometer
UV/Vis
Ingredients:
Polyethylene
glycol (PEG) 1000
Polyethylene
glycol (PEG) 6000
Paracetamol
PROCEDURES
1.
A paracetamol stock saturated
solution was prepared (10g in 5ml distilled water)
2.
Paracetamol suppository (10g)
was prepared by using the following formulation:
Ingredients ( g )
|
Paracetamol stock
solution (g)
|
Total ( g )
|
|||
Suppository
|
Group
|
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 was shaped by using the suppository-mould.
The shape, texture and colors of the suppository were explained and compared with others.
The suppository was shaped by using the suppository-mould.
The shape, texture and colors of the suppository were explained and compared with others.
4.
One suppository was added into
a beaker containing distilled water (10ml, 37°C) and the time needed to
dissolve it was determined.
PEG 6000 (g)
|
0
|
3
|
6
|
9
|
Average time taken to melt (min)
|
38.49
|
42.78
|
39.68
|
74.38
|
5.
Another one suppository was
filled into the dialysis bag and the two ends were tied properly. The bag was
added into the 100ml beaker containing distilled water (50ml) which was heated
to temperature 37°C.
6.
Every 5 minutes, one aliquot
sample (3 – 4 ml) was pipette and the release of Acetylsalicylic acid from the
cream base was determined by using spectrometer UV-visible. The distilled water
was stirred with glass rod before the sample was taken.
Time(min)
|
Visible-UV Absorption
|
|||||||||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
||
UV absorption on 520nm
|
Group 1
|
0.003
|
0.006
|
0.053
|
0.054
|
0.028
|
0.029
|
0.050
|
0.012
|
0.008
|
0.012
|
0.022
|
0.005
|
0.018
|
Group 5
|
0.012
|
0.016
|
0.016
|
0.026
|
0.019
|
0.018
|
0.021
|
0.021
|
0.021
|
0.097
|
0.020
|
0.022
|
0.024
|
|
Group 2
|
0.001
|
0.018
|
0.090
|
0.039
|
0.105
|
0.096
|
0.044
|
0.088
|
0.0048
|
0.098
|
0.052
|
0.051
|
0.051
|
|
Group 6
|
0.025
|
0.006
|
0.006
|
0.008
|
0.007
|
0.010
|
0.010
|
0.009
|
0.009
|
0.032
|
0.013
|
0.012
|
0.015
|
|
Group 3
|
0.026
|
0.032
|
0.029
|
0.024
|
0.032
|
0.037
|
0.067
|
0.042
|
0.047
|
0.052
|
0.055
|
0.058
|
0.060
|
|
Group 7
|
0.004
|
0.006
|
0.026
|
0.030
|
0.042
|
0.045
|
0.064
|
0.063
|
0.075
|
0.083
|
0.099
|
0.083
|
0.100
|
|
Group 4
|
0.066
|
0.075
|
0.080
|
0.084
|
0.087
|
0.091
|
0.093
|
0.095
|
0.094
|
0.102
|
0.106
|
0.107
|
0.109
|
|
Group 8
|
0.004
|
0.005
|
0.007
|
0.005
|
0.006
|
0.006
|
0.006
|
0.009
|
0.007
|
0.007
|
0.009
|
0.012
|
0.014
|
|
QUESTION
1.
Compare the physical appearance of the suppository formed and
discuss.
Group
|
Paracetamol Stock Solution (ml)
|
Substance (g)
|
Physical appearances
|
|||||
PEG
1000
|
PEG
6000
|
Shape
|
Texture
|
Hardness
|
Colour
|
|||
I
|
1
|
1
|
9
|
0
|
Torpedo-shaped
|
Dull and smooth
|
Soft
|
White
|
5
|
Torpedo-shaped
|
Dull and smooth
|
Hard
|
White
|
||||
II
|
2
|
1
|
6
|
3
|
Torpedo-shaped
|
Shiny, smooth, have odour
|
Hard
|
White
|
6
|
Torpedo-shaped
|
Dull and smooth
|
Soft
|
White
|
||||
III
|
3
|
1
|
3
|
6
|
Torpedo-shaped
|
Dull and smooth
|
Hard
|
White
|
7
|
Torpedo-shaped
|
Dull, sticky and smooth
|
Hard
|
White
|
||||
IV
|
4
|
1
|
0
|
9
|
Torpedo-shaped
|
Dull and smooth
|
Hard
|
Colourless white
|
8
|
Torpedo-shaped
|
Shiny and rough
|
Hard
|
Colourlesswhite
|
||||
In this experiment, all the suppositories formulated
are torpedo-shaped. Different quantities
of PEG 1000 and PEG 6000 for each group will lead to the formation of
suppositories with different physical characteristics.
Based on the observation that has been carried out,
suppositories from Group I has the highest intensity of white colour (chalky
white) compared to the other groups. The intensity of white colour is
decreasing to nearly colourless from Group II to Group IV due to the presence
of small amount of PEG 1000 and increasing amount of PEG 6000. Since the active
ingredient that is used in the experiment is paracetamol which is white in
colour, the colour of the suppositories produce will be white but differ in the
transparency degree. The formulation with the lowest amount of PEG 1000 is more
transparent compared to the others.
As for texture, most suppositories formed are very greasy but least shining compared to
the other suppositories. This is due to the presence of high amount of PEG
1000. Suppositories from our group which is Group I are the most greasy due to
presence of high amount of PEG 1000 and absence of PEG 6000. Suppositories from
Group IV is the hardest of all. This is because the hardness of PEG increases
with increasing molecular weight. PEG 6000 has bigger molecular weight compared
to PEG 1000. In other words, the higher
the quantity of PEG 6000 in a formulation, the less greasy the suppository will
be. As for hardness, we can conclude that the higher quantity of PEG 1000
(lower quantity of PEG 6000), will produce softer suppository.
2. Plot a graph of time
needed to melt suppository against amount of PEG 6000 in formulation. Compare
and discuss the result.
GROUP
|
TIME TAKEN TO MELT SUPPOSITORY (min)
|
1
|
40.45
|
2
|
36.56
|
3
|
46.36
|
4
|
43.32
|
5
|
32.52
|
6
|
49.06
|
7
|
33.00
|
8
|
31.06
|
AMOUNT OF PEG 6000 (g)
|
0
|
3
|
6
|
9
|
MEAN TIME (min) (x ± SD)
|
36.49 ± 3.97
|
42.81 ± 6.25
|
39.68 ± 6.68
|
37.19 ± 6.13
|
 |
Polyethylene glycol (PEG) acts as
suppository base in this formulation. This
suppository do not melt at body temperature but rather dissolve slowly in the
body’s fluids. The suppository will become
more solid as the amount of PEG 6000 increase. So, the time taken to melt the
suppository will be longer as the amount of PEG 6000 increase. When there is no
PEG 6000 in the formulation, the mean time to melt the suppository is 36.49
minutes. For 3 g of PEG 6000, the time is 42.81 minutes which it get longer.
For 6 g and 9 g of PEG 6000, the time is 39.68 and 37.19 minutes respectively.
The time get faster after 3 g of PEG 6000. However, the time pattern should be
increase as the amount of PEG 6000 increase.
This may be due to some error happen while conducting the
experiment. For example, the suppository may be not solidified enough when
taken out from the refrigerator. The unsolidified suppository will dissolve
faster. Stirring the beaker also may affect the result as stirring can increase
the melting time.
3. Plot the graph UV
absorption against time (procedure 6). Give comments
UV absorption
|
|||||||||||||
Time (min)
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
UV absorption on 520 nm
|
0.003
|
0.006
|
0.053
|
0.054
|
0.028
|
0.029
|
0.050
|
0.012
|
0.008
|
0.012
|
0.022
|
0.005
|
0.018
|
The graph shows the amount of UV being
absorbed when the releasing of paracetamol in distilled water against time. It
shows a non-constant result where there is up and down based on data obtained.
This is deviated than the theoretical one which the result is constantly
increase when increasing time. Error has been occurring during conducted the
experiment. Firstly, before taking the sample to be examined on UV
spectrometer, distilled water are not completely stirred. Next is the
suppository made is not pure thus causing the releasing of paracetamol in
suppository is not very accurate. The time taken the sample is not accurate 5
minutes interval. This will cause the exact value of paracetamol release in
correct time is not obtained.
4. Plot the
graph of UV absorption against time for the suppository formulation with
different compositions. Discuss and compare the results.
There are 4 parameters
of an in vitro suppository drug release, which are temperature, contact
area, release medium and membranes. Throughout the experiment, 37oC
is used for the experiments of drug release from the suppositories.
Measurements of drug release at 37oC may become an over estimation
due to the differences in melting range of the suppositories.
There
is no apparatus to mimic the contact area between the suppository and the
rectal mucosa. This is important in determining the rate of drug release of the
suppository. As long as this is not developed, the results are not tailor-made
for the real condition, inaccurate results may be produced. Distilled water is
considered as the release medium in this experiment. However, we should know
that there is no ideal solution yet due to the problem of choosing a suitable
volume and composition of the release medium that suits the condition in the
rectal area. The “membrane” we used in this experiment is the dialysis bag.
This may come with an enormous drawback as the release measured in the outer
compartment is not equal to the actual release that is taking place in the
inner compartment. The membrane may form a resistance to passing drug
molecules. The actual release may be underestimated.
Theoretically, different composition of
suppository base will affect the drug release from the suppository. Suppository
(in this case Suppository IV) which contains the highest amount of PEG 6000 has
the highest molecular weight and thus lowest drug releasing rate. This is due
to the formation of strong hydrogen bond between the molecules in the
suppository. Therefore, more time is needed to break the bond and release the
drug. So, the release rate of drug and UV absorption should be the lowest
compare to the other suppositories which have lower amount of PEG 6000. For Suppository I which has the highest
amount of PEG 1000 and the lowest amount of PEG 6000, the rate of drug released
from the base should be the highest. This is due to the weakest hydrogen bond
formed between the molecules. Thus drug is easier to be released as less time
is needed to break the bond and release the drug.
From the graph plotted, the UV absorption of
Suppository III is the highest while the lowest UV absorption is shown by
Suppository I. From this we can interpret that the release rate of paracetamol
is highest in Suppository III while lowest in Suppository I among all
suppositories. However, the results obtained are deviate from the theory. This
may due to the errors that occur in this experiment which include the size of
the suppositories formed, the problem of the UV spectrophotometer and may be
the PEG used are contaminated.
5. What are the function of every ingredients in the formulary? and how the usage of PEG 6000 and PEg 1000 influence physical properties of suppositories formulation.
Paracetamol act
as active ingriedient for this suppositories dosage form. PEG or polyethylene glycol, act as a base for
this suppositories. PEG is a base that miscible with water and mucous secretion
that has a wide range of hardness and melting point. Sometimes, the formulation
of suppositories will use only one PEG with the same molecular weight, but commonly,
formulas call for compound for two or more molecular weight with various ratios
in order to get satisfactory hardness and dissolution time. The
hardness of polyglycols
increases with increasing molecular
weight, however the melting range
goes up to a maximum value of 60 degree. As the molecular weight is higher the
water solubility is lower. PEG suppositories do not melt at body temperature
but rather will dissolve in the body’s fluis. Thus perfect ratio of PEG is
needed. Having high melting point, permits a slower release of the medication
form the base once the suppository has been inserted in body.
CONCLUSION
Suppository with high content of PEG
1000 will have dull and smooth texture, soft and white color. Suppository with
high content of PEG 6000 is hard and colorless white. High content of PEG 6000
also will make the suppository to take longer time to melt and have lowest drug
releasing rate.
