Objectives:
To study the effect of different composition of base
on the physical characteristic of suppositories.
Introductions:
Suppositories are designed for anal administration
and usually consist of the active drug and a base which is designed to melt at
room temperature. Once the suppository has been rectally administered the base
will then break down and the drug will be released. Good bases are not toxic, no irritation, will not
interact with other drugs and also easy to be mould into a suppository.
Different composition on base will affect the rate and limit of release of the
drug from the suppository.The formulation and design is no
more complex than this.Most suppositories are prescribed for local effects. The
anal route however provides an excellent route for drug absorption and
therefore can be used in patients with swallowing difficulties or for drugs
where avoidance of first past effect is preferable. For this reason it is
important to check the bioavailability of a suppository compared to a tablet
when swapping between the two. 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:
Electronic balance, Weighing boat, Spatula, 50 ml
beaker, 100 ml beaker, Hotplate, 5 ml
measuring cylinder, Suppository mould, Water bath (37 °C), Slape, Mortar and
pestle, Dialysis bag (10cm), Threads, Glass rod , 5 ml Pipette and pipette
bulb, Plastic Cuvettes, UV/Vis spectrophotometer.
Materials:
Polyethylene glycol (PEG) 1000, Polyethylene glycol
(PEG) 6000, Paracetamol
Procedure:
1.
Saturated Paracetamol stock (10g in 5 ml distilled water) water was
prepared.
2.
10g Paracetamol suppository was prepared using following formula:
Suppository
|
Group
|
Ingredient (g)
|
Paracetamol stock
|
Total amount (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.
Suppository mould was used to produce suppository shape. The
textures, shape and colour were described and differentiate.
4.
One suppository produced was placed into the beaker that contained
distilled water (10ml, 37°C) and the time for suppository to dissolve was
recorded.
5.
Next, one suppository was placed into the dialysis bag and the end of
the bag was tightly tied. The dialysis bag was then put into beaker that
contains 50 ml distilled water at 37°C.
6.
At the interval of 5 minutes, 3ml of sample was pipette and the
release of paracetamol from suppository was determined using UV visible
spectrometer. The distilled water was stirred first before the sample was
taken.
Time (min)
|
UV absorption
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
UV absorption at 310nm
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Results:
Result
1
Suppository
|
Shape
|
Teksture
|
Color
|
I
|
Torpedo
|
Smooth,
hard, oily
|
Even
white
|
Torpedo
|
Smooth,
hard, oily
|
Even
white
|
II
|
Torpedo
|
Smooth,
hard
|
Even
white
|
Torpedo
|
Smooth,
hard
|
Even
white
|
III
|
Torpedo
|
Smooth,
hard
|
Uneven
white
|
Torpedo
|
Smooth,
hard, sticky
|
Milky
white
|
IV
|
Torpedo
|
Smooth,
hard, oily
|
Uneven
white
|
Torpedo
|
Smooth,
hard
|
Uneven
white
|
Result
2
PEG
6000 content (g)
|
Time
taken for the suppository to completely melt (min)
|
Average
(min) (x ± SD)
|
I
|
II
|
0
|
31
|
54
|
42.5
± 16.26
|
3
|
27
|
27
|
27.0
± 0.00
|
6
|
40
|
50
|
45.0
± 7.07
|
9
|
73
|
65
|
69.0
± 5.66
|
Result
3
Time
(min)
|
Average
UV absorption at 520 nm (x ± SD)
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
Suppository
|
I
|
0.015
|
0.028
|
0.073
|
0.032
|
0.033
|
0.018
|
0.021
|
0.022
|
0.024
|
0.023
|
0.026
|
0.092
|
0.035
|
0.015
|
0.038
|
0.089
|
0.093
|
0.118
|
0.101
|
0.107
|
0.141
|
0.125
|
0.100
|
0.136
|
0.118
|
|
Average
|
0.015
|
0.033
|
0.081
|
0.063
|
0.076
|
0.060
|
0.064
|
0.082
|
0.075
|
0.062
|
0.081
|
0.105
|
|
SD
|
0.000
|
0.007
|
0.011
|
0.043
|
0.060
|
0.059
|
0.061
|
0.084
|
0.071
|
0.054
|
0.078
|
0.018
|
|
II
|
|
0.088
|
0.028
|
0.020
|
0.100
|
0.069
|
0.048
|
0.094
|
0.089
|
0.096
|
0.127
|
0.115
|
0.103
|
|
0.206
|
0.133
|
0.132
|
0.053
|
0.048
|
0.048
|
0.047
|
0.042
|
0.118
|
0.048
|
0.054
|
|
Average
|
|
0.147
|
0.081
|
0.076
|
0.077
|
0.059
|
0.048
|
0.071
|
0.066
|
0.107
|
0.088
|
0.085
|
|
SD
|
|
0.083
|
0.074
|
0.079
|
0.033
|
0.015
|
0.000
|
0.033
|
0.033
|
0.016
|
0.056
|
0.043
|
|
III
|
0.064
|
0.071
|
0.087
|
0.098
|
0.101
|
0.111
|
0.115
|
0.119
|
0.121
|
0.111
|
0.125
|
|
|
0.014
|
0.017
|
0.019
|
0.022
|
0.024
|
0.028
|
0.028
|
0.028
|
0.030
|
0.034
|
0.034
|
0.036
|
0.038
|
Average
|
0.039
|
0.044
|
0.053
|
0.060
|
0.063
|
0.070
|
0.072
|
0.074
|
0.076
|
0.073
|
0.080
|
|
|
SD
|
0.035
|
0.038
|
0.048
|
0.054
|
0.054
|
0.059
|
0.062
|
0.064
|
0.064
|
0.054
|
0.064
|
|
|
IV
|
0.003
|
0.010
|
0.014
|
0.018
|
0.019
|
0.019
|
0.021
|
0.024
|
0.026
|
0.026
|
0.024
|
0.028
|
0.026
|
0.017
|
0.021
|
0.037
|
0.047
|
0.049
|
0.053
|
0.057
|
0.059
|
0.059
|
0.063
|
0.065
|
0.070
|
0.072
|
Average
|
0.010
|
0.016
|
0.026
|
0.033
|
0.034
|
0.036
|
0.039
|
0.042
|
0.043
|
0.045
|
0.045
|
0.049
|
0.049
|
SD
|
0.010
|
0.008
|
0.016
|
0.021
|
0.021
|
0.024
|
0.025
|
0.025
|
0.023
|
0.026
|
0.029
|
0.030
|
0.033
|
Question and Discussion
1.
Compare
the physical appearance of the suppositories and give explanation.
Suppository
|
Shape
|
Teksture
|
Color
|
I
|
Torpedo
|
Smooth,
hard, oily
|
Even
white
|
Torpedo
|
Smooth,
hard, oily
|
Even
white
|
II
|
Torpedo
|
Smooth,
hard
|
Even
white
|
Torpedo
|
Smooth,
hard
|
Even
white
|
III
|
Torpedo
|
Smooth,
hard
|
Uneven
white
|
Torpedo
|
Smooth,
hard, sticky
|
Milky
white
|
IV
|
Torpedo
|
Smooth,
hard, oily
|
Uneven
white
|
Torpedo
|
Smooth,
hard
|
Uneven
white
|
Based on
the result above, we can observe that the ratio between PEG 1000 and PEG 6000
can determine the physical properties of suppositories. As the content of PEG
1000 is increased, the suppositories produced are more oily, sticky and soft.
This is because PEG 1000 is more hydrophobic compare to PEG 6000.
While,
as the content of PEG 6000 is increased, the suppository produced are more
solid and non-sticky. This
could be explained as the physicochemical characters of PEG 6000 forms more
strong and stable hydrogen bonds in the suppository compared to PEG 1000. PEG
6000 is higher molecular weight compare to PEG 1000. Thus, it also has a lot of
hydroxyl groups which can form numerous hydrogen bonds between the molecules of
the PEG 6000 and the molecules of Paracetamol. Hence, we could see an increase
in the hardness of the suppositories in line with the increasing amount of PEG
6000.
Besides
that, from suppository I to
IV, the formulation reduced
in PEG 1000 and increased in PEG 6000 content which causes the color change
from clear, even white to opaque, uneven white. Suppository formed by higher amount of lower molecular
weight polyethylene glycol is more transparent and is more lustrous in nature.
Due to higher amount of PEG 6000 being used, suppositories formed will appear
in white color. This is shown in Suppository II, III and IV.
As the mould made for suppositories
is bullet shaped, thus all four suppositories produced are bullet shaped. This
torpedo shape is suitable for a suppository according to its route of
administration. As a conclusion, we must specify the amount of PEG 1000 and PEG
6000 to produce an ideal suppository. The ideal suppositories are melt in body
temperature, not too stick or too rough, and balance in hardness and
smoothness.
2.
Plot a graph of the average time taken for the suppository to melt against the
amount of PEG 6000 used in the formulation. Compare and discuss the results
obtained.
PEG
6000 content (g)
|
0
|
3
|
6
|
9
|
Average
(min)
(x
± SD)
|
42.5
± 16.26
|
27.0
± 0.00
|
45.0
± 7.07
|
69.0
± 5.66
|
Based on the graph, the average melting point of
suppository at body temperature 37C is increases as the content of PEG 6000
increases from 3g to 6g of PEG 6000 content. This is true according to the
theory where it state that the melting point of suppository is proportional to
their molecular weights which dominant to PEG 6000.
Therefore,
increase amount of PEG 6000 used will increase melting point as well as time
taken for formulation to melt. Besides that, the amount of PEG 1000 also plays
a role. This is because the melting point of PEG 1000 is about 37-40 °C which
is close to human body temperature; 37.5 °C, thus it will easily melt once
inserted into rectum. Hence,
theoretically increased amount of PEG 1000 in the formulation will decreased
the melting point of suppository until the temperature around body temperature.
However, at 0g of PEG 6000 content,
the melting point is slightly higher than 3g of PEG content, thus the graph
starts with decreasing slop from 0g to 3g and then, increase proportionally
from 3g to 9g of PEG 6000 content. The higher melting point of 0g compared to
3g might be due to impurities in the formulation or errors occurred during the
experiment.
The
errors can occur during measuring, and transferring of the ingredient during
making of suppository. Besides that, possibility of suppository does not solid
enough when we taken out from the refrigerator as the unsolidified suppository
made it easier to be dissolved in water bath. The heating process using water
bath also may produce this result. Some of the group might stir the beaker
containing suppository which make it faster to dissolve. Lastly, the possible
errors are wrongly observe the finish melting time of the suppository, dialysis
beg did not seal tightly and wrongly watch the time.
3. Plot a graph of UV
absorption against time. Give reasons.
In this experiment, suppository was put inside a
dialysis bag then immersed into a beaker containing distilled water with
temperature maintained at 37⁰C
which is similar to our body temperature. This is to determine the absorption
rate of drug in our body after administration of suppository via rectum route.
The release of the drugs from the suppository involved the diffusion mechanism.
The UV spectrometer measures the release of paracetamol from the suppository in
the dialysis bag to the distilled water. The graph above showed the change of
UV absorption with the amount of Paracetamol released into distilled water as
the time passed. From the graph of UV absorption against time, the extent of
drug release was assessed from the total amount of drug present in the
dissolution medium for every 5 minutes interval. At time=0, UV absorption
observed was 0.01. With increasing of time, UV absorption also increased. This
showed that the amount of drug released was increased too. Hence, there is a
direct proportional relationship between time and drug release. As the
experiment proceeded, the content in the dialysis bag tended to become isotonic
to the distilled water as amount of paracetamol was reduced after moving to the
distilled water. This resulted in the reduced gradient of the graph when time
passesd by. If the experiment is continued beyond 60 minutes, it may result in
a straight line graph as the concentration of paracetamol in the distilled
water equals to the concentration of paracetamol at the dialysis bag.
4.
Plot graph of UV absorption against time for the suppository formulation with
different compositions. Discuss and compare the results.
In
the experiment, dialysis tube had been use to determine the ability of the
paracetamol of suppository to pass through the membrane and enter into the
water. The amount of the sample that passed through the dialysis tube is
measured by using the ultraviolet spectrophotometry. Dialysis tube indicates
the human’s biological barrier. Based on the results, we can see that UV
absorption at 520 nm is increasing with time for each of the suppositories.
Increasing in UV absorption indicates that there is increasing in the numbers
of particle of the suppositories diffuse through the dialysis tube membrane.
From
the graph above, the value that has been obtained is not accurate because in
this experiment, the suppository I which has highest drug release (given as the
UV absorption) release the drug in a fluctuation trend. Suppository I should be the highest among the
four suppositories since it has the highest amount of the PEG 1000. The UV
absorption will increase with time until it reaches a plateau stage where the
entire drug has been released. Suppository II shows the higher rate of drug
release than suppository III as it has higher composition of PEG 1000 and lower
amount of PEG 6000 that slow the release rate of drug. This obeys to the
theory.
Water
solubility of the drug suppository increases as the molecular weights of PEG
decrease due to the water absorbing properties of PEG. Thus, the highest rate
of release is expected for suppository I due to the lowest proportion or amount
of PEG 6000 in the formulation In theory, the hardness of the polyethylene
glycol will increase with increasing molecular weight. So, as the suppository
becomes harder, it should required longer time to dissolve the drug and passing
through the dialysis tube membrane. Polyethylene glycol with molecular weight
from 600 to 1000 is presence in the semisolid form and molecular weight higher
than 1000 is wax-like form. Therefore, suppository I should has the highest UV
absorption.
High
proportion of high polyethylene glycol produce suppository which release drug
slowly and also brittle. Suppository IV has the highest proportion of PEG 6000
which will produce the hard suppository that difficult to dissolve. Higher
contents of PEG 6000 will give the slowest releasing rate of drug due to the
strong hydrogen bond among molecules PEG 6000 with molecules Paracetamol. It released the drug slowest. The result of
the experiment can be considered same as the theory. In order to prepare less
brittle suppository with release drug more readily, high molecular weight
should be mixing with medium or low molecular weight of polyethylene glycol.
Since
PEG is nonionic substances, they are quite soluble in hard water or in other
aqueous solution of various salts. Suppositories can be formulated with much
higher melting point to be melting at body temperature and dissolve in body
fluids. Graph become not accurate may be because of the error that has been
done during the experiment. May be error occur in taking sample by pipette to
measure dispersion of paracetamol using spectrometer UV-visible.
5.
What is the function of each ingredient that is used in the preparation of
these suppositories? How does the usage of different content of PEG 1000 and
PEG 6000 affect the physical properties of suppository formulation and rate of
releasing of drug from it?
Paracetamol
is active ingredient in the suppositories. Paracetamol is used as analgesic and
antipyretic. It appears as white, odourless and light powder. PEG 1000 and PEG
6000 are the bases for the active ingredient, paracetamol of the suppository.
They allow a smoother drug delivery of the suppository into the rectal. They
also allow the absorption of paracetamol by the membrane to occur. A suitable
combination of PEG allows an optimum drug releasing to occur, in which the drug
will not be held strongly in the base and can be easily released. This is
important to allow an optimum drug bioavailability to take place as the drug
can be absorbed by mucosa membrane of the rectal.
The
different amount of PEG 1000 and PEG 6000 used can influence the physical
characteristic and the release rate of drug from suppository base. Higher
amount of PEG 6000 increase hardness of suppository formed due to stronger
hydrogen bond formed between molecules. Due to this strong hydrogen bonding,
the drug release rate will be lowered. Using higher amount of PEG 1000 will
result in softer suppository. This is due to weaker hydrogen bond formed
between the molecules. Lipophilicity of PEG 1000 is higher, thus result in
greasier suppository. Drug release will be faster because the bond formed is
weaker.
Different characteristic of suppositories can be formed by varying
amount and molecular weight of PEG used. Therefore by varying the combinations
of PEG, we can obtain desired consistency and characteristic of suppositories.
A balance of lipophilicity and hydrophilicity of suppository base can be
achieved by this combination. Thus, bases that fulfill desired characteristics
can be used in formulation and this will lead desired rate release of drug from
the suppository base.
Conclusion:
The
different amount of combination of PEG 1000 and PEG 6000 in the suppository
preparation affects the physical characteristics e.g. greasiness texture, and
shape of the suppository as well as the rate of release of the active
ingredient.
Appendix
PEG 6000 is heated until molten mixture is formed.
Paracetamol is added into molten mixture and
stirred.
The molten suppositories is formed.
The suppository mould is lubricated by using
Parraffin Oil.
Suppositories formulation is added into the
suppository mould.
The suppositories is cooled by placing the mould in
the refrigerator.
The shape, texture and color of the suppository are
observed and recorded.
The suppository was placed inside the dialysis bag
and both ends of the dialysis bag are tied tightly.
The dialysis bag is placed in a beaker which is the
placed inside the water bath at 37oC.
Reference:
1.
Pharmaceutics:
the science of dosage form design,
Aulton, M.E.2002
2. David Troy. 2000.
Remington: The Science and Practice of Pharmacy. Lippincott Williams & Wilkins. 21th edition. Page
1079-1080