TITLE: Evaluation of the effect of different formulation on suppository characteristics.
AIM: To study the effect of different composition of base on the physical characteristic of suppositories.
INTRODUCTION:
A suppository is a drug delivery system that is inserted
into the rectum (rectal
suppository), vagina (vaginal
suppository) or urethra (urethral suppository), where it dissolves or
melts and is absorbed into the blood stream. They are used to deliver both
systemically and locally acting medications. Suppositories are medicated, solid
bodies of various sizes and shapes suitable for introduction into body cavities
through rectal administration. Good suppository will melt after the rectal
administration and release the drug either topically or systematically.
The medicament is incorporated into a base such as PEG which slowly
dissolves in the mucous secretions. The ideal suppository base should be
non-toxic, non-irritating, inert, compatible with medicaments, and easily
formed by compression or moulding. Different composition of bases will affect
the rate and limit of release of the drug 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
Analytical balance
Weighing boats
Spatula
50ml and 100ml beakers
Hotplate
5ml measuring cylinder
Suppository mould set
Water bath 37oC
Dialysis bag
Thread
Glass rod
5ml pipette and pipette bulb
Plastic cuvette
UV spectrophotometer
MATERIAL
Polyethylene glycol (PEG) 1000
Polyethylene glycol (PEG) 6000
Paracetamol
Distilled water
Liquid paraffin
PROCEDURE
1. 10g of suppository is prepared using the
formulation below:
Suppository
|
Group
|
PEG 1000
(g)
|
PEG 6000
(g)
|
Paracetamol (g)
|
Total
(g)
|
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
|
2. The suppository is moulded using
the suppository mould. The shape, texture and colour of the suppository is observed and discussed.
3. One suppository is placed into a
beaker containing 10ml of distilled water (10ml, 37˚C ) and the time required for the suppository to melt is recorded.
4. One suppository is inserted into
a dialysis bag and both ends are tied neatly, as shown in the figure
below. It is then placed into a beaker containing 50mL of distilled water which
is then placed
inside the water bath at 37oC.
5. The sample is pipetted (3- 4mL) in 5
minutes interval and the release of Paracetamol from the suppository
is determined using the UV-visible spectrometer. The distilled water must be stirred
first before the sample is taken.
1. Compare
the physical appearances of suppositories
formed and give comments.
FORMULATION
|
GROUP
|
SHAPE
|
TEXTURE
|
COLOUR
|
I
|
1
|
Torpedo
|
Smooth, hard, oily
|
Even white
|
5
|
Torpedo
|
Smooth, hard, oily
|
Even white
|
|
II
|
2
|
Torpedo
|
Smooth, hard
|
Even white
|
6
|
Torpedo
|
Smooth, hard
|
Even white
|
|
III
|
3
|
Torpedo
|
Smooth, hard
|
Uneven white
|
7
|
Torpedo
|
Smooth, hard, sticky
|
Milky white
|
|
IV
|
4
|
Torpedo
|
Smooth, hard, oily
|
Uneven white
|
8
|
Torpedo
|
Smooth, hard
|
Uneven white
|
The table above shows the comparison between the
physical appearances of suppositories in those formulations based on the
different quantities of PEG 1000 and PEG 6000 in the suppository base mixtures
for each group. Based on the
result obtained, the shapes of all the formulation of suppositories are the
same shape which are torpedo-shape since that all the suppositories were
prepared in the same suppository mould.
For the texture,
formulation with the highest amount of PEG 1000,
which means that it has the lowest quantity of PEG 6000 shows the greasiest
surface and smooth compared to the other suppositories. Meanwhile, for the
formulation with the lowest amount of PEG 1000 and the highest amount of PEG
6000, the suppository formed is the hardest and least greasy. 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 which has higher molecular weight compare to PEG 1000 has a lot of hydroxyl groups which can form numerous
hydrogen bonds between the molecules of the PEG 6000 and the molecules of
Paracetamol. Therefore, we can conclude that the higher the amount of PEG 6000,
the hardness of the suppositories also will increase.
Then, for the colours of all
suppositories are white as the active ingredient used is paracetamol which has
white in colour. The intensity of these suppositories are undistinguishable
where there are no effect on the colour intensity of the suppository since the
colour obtained from all formulation is the same even with different quantities
of the PEG 1000 and PEG 6000 but the differences is in the transparency degree.
The formulation with the lowest amount of PEG 1000 is more transparent compared
to the others.
2.
Plot a graph of the time required to melt the suppository against PEG 6000
content in the formulation. Compare and discuss the result.
Amount of PEG 6000 (g)
|
0
|
3
|
6
|
9
|
||||
Groups
|
1
|
5
|
2
|
6
|
3
|
7
|
4
|
8
|
Time (min)
(x ± SD)
|
31
|
54
|
27
|
27
|
40
|
50
|
73
|
65
|
42.5 ±
16.26
|
27 ± 0
|
45 ± 7.07
|
69 ± 5.66
|
Based on the graph above, it is shown that the time required to melt suppositories are varies in each formulation that contain different amount of Polyethylene glycol (PEG) 6000. PEG 6000 is a suppository base that is chemically stable, nonirritating, miscible with water and mucous secretions, and can be formulated, either by molding or compression, in a wide range of hardness and melting point. Thus, PEG 6000 can make the suppository more solid.
Polyethylene
glycol suppositories do not melt at body temperature but rather dissolve slowly
in the body’s fluids. Therefore, the base need not be formulated to melt at
body temperature. Thus, it is possible, in fact routine, to prepare
suppositories from polyethylene glycol mixtures having melting points considerably
higher than body temperature. This property permits a slower release of the
medication from the base once the suppository has been inserted, and permits
convenient storage of these suppositories without need for refrigeration and
without danger of their softening excessively in warm weather.
Furthermore,
their solid nature permits slow insertion without fear that they will melt in
the fingertips (as cocoa butter suppositories sometimes do). Because they do
not melt at body temperature but mix with mucous secretions upon dissolution,
polyethylene glycol–based suppositories do not leak from the orifice, as do
many cocoa butter–based suppositories. Polyethylene glycol suppositories that
do not contain at least 20% water should be dipped in water just before use to
avoid irritation of the mucous membranes after insertion. This procedure
prevents moisture being drawn from the tissues after insertion and the stinging
sensation.
Theoretically, the time required to melt suppositories are
increases gradually as the amount of PEG 6000 increases. This is because high
content of PEG 6000 will make the suppository become harder and solidify. Thus,
it will take time to melt when inserted into distilled water (37ºC).
Suppository with 9g of PEG 6000 has longer time to melt compared to other
suppositories. However, in this experiment, there were a slight error has
occurred as we can see on the suppository with 0g of PEG 6000. The time
required for it to melt is longer compared to suppository with 3g of PEG 6000.
There might be some errors that occurred when conducting the experiment. The
possibilities of errors might be due to wrongly measured the amount of PEG
6000. Moreover, the temperature of the water bath may be not fixed at 37ºC
which can cause the result not accurate.
3.
Plot a graph UV absorption against time.
Give explaination.
Time (min)
|
UV-Visible Absoption at 520nm
|
0
|
0.015
|
5
|
0.038
|
10
|
0.089
|
15
|
0.093
|
20
|
0.113
|
25
|
0.101
|
30
|
0.107
|
35
|
0.141
|
40
|
0.125
|
45
|
0.100
|
50
|
0.136
|
55
|
0.118
|
60
|
0.103
|
The graph above shows the UV absorption at 520nm for suppository 1 that contains 9g of PEG 1000 and 1g of Paracetamol. This graph shows fluctuates which the line goes up and down. The graph should give a sigmoidal shape as the suppository will dissolve and release slowly at body temperature, 37˚C. The drugs released will increased the concentration of drugs in the water until the concentration reached equilibrium or isotonic as the concentration of the drugs in the dialysis bag same to the concentration of drugs in the water. When the equilibrium achieved the graph should be constant because there is no net movement of drugs.
From
this graph, it keep going increase until it drop at 25th minutes.
Then the graph elevated again until the 35th minutes and then drop
at the 40th to 45th minutes before it strongly increase
at 50th minutes and back to fall down at the 55th and 60th
minutes. This graph shows big deviates from the theoretical principle which due
to many errors may occurred. The errors may occurred due to the presence of
impurities during prepare the suppositories, parallax error, the dialysis bag
not been tied correctly and also due to the distilled water not stirred
properly before collect the sample to measured the UV visible absorption. These
errors will affect the results obtained.
4. Plot a graph of UV absorption for different
composition of suppository formulations against time. Compare and explain the
results.
Time
(mins)
|
Average
UV absorption at 520 nm
|
||||||||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
I
|
0.015
|
0.020
|
0.044
|
0.024
|
0.024
|
0.017
|
0.018
|
0.019
|
0.020
|
0.019
|
0.021
|
0.029
|
0.025
|
II
|
0.015
|
0.147
|
0.081
|
0.167
|
0.077
|
0.059
|
0.048
|
0.071
|
0.066
|
0.107
|
0.088
|
0.085
|
0.077
|
III
|
0.039
|
0.044
|
0.053
|
0.057
|
0.061
|
0.065
|
0.070
|
0.072
|
0.075
|
0.078
|
0.073
|
0.072
|
0.082
|
IV
|
0.010
|
0.016
|
0.026
|
0.031
|
0.034
|
0.024
|
0.037
|
0.041
|
0.043
|
0.045
|
0.045
|
0.050
|
0.050
|
Different suppository base compositions
will have different effects on the drug release rate over time. In this
experiment, we varied the ratio amount of PEG 1000 and PEG 6000 in each of the
suppository. Suppository I has the
highest amount of PEG 1000 and none PEG 6000. According to the theory, it
should be showing the highest drug releasing rate as well as the UV absorption.
This is due to lesser hydroxyl group present in PEG 1000. Thus, there are less
strong hydrogen bond formed between the molecules of PEG 1000 and molecules of
paracetamol. Little energy would be needed to break the bonds to release the
drug. Hence, higher releasing rate is expected and it would cause the UV
absorption to be higher. So, from suppository I to suppository IV, the average
IV absorbance should increase all the time following this order as the amount
of PEG 1000 decreasing while amount of PEG 6000 increasing in this order.
Suppository IV has more hydrogen bonding
formed between the molecules of PEG 6000 as it has more hydroxyl groups present
in it and the molecules of the paracetamol when they are mix together and
formed a suppository. It has the highest molecular weight and this would cause
a lower drug releasing rate. Therefore, a longer time and higher energy is
needed in order to break down the strong hydrogen bond and subsequently release
the drug. This will further lower the UV absorption. Apart from that,
suppository II and suppository III has intermediate UV absorption. Suppository
III has lower UV absorption than Suppository II as Suppository II has higher
PEG 1000 but lower PEG 6000 than Suppository III. Thus, there are less hydrogen
bond formed between the Suppository II bases and paracetamol. Less energy would
be needed to break the bonds to release the drug. Hence, it would have a higher
releasing rate than Suppository III and this would cause the UV absorption of
Suppository II to be higher than Suppository III.
Based on the graph, we can see that
Suppository III has the highest UV absorption, while, Suppository IV has lowest
UV absorption rate, which indicates that it has lowest drug releasing rate.
This did not comply with the actual theory. Besides that, the graph showed
deviated much in comparison between results of each two groups. It is due to
many errors arisen in the experiment. These errors can be due to the improper
method of compounding, non-homogenous dispersion of Paracetamol in the PEG
suppository base, inaccuracy of the UV spectrometer, and so on. Other errors
that may occur include inconsistency in temperature which may affect the drug
release from the suppository, the sample in the beaker did not stir well before
pipette out from the solution or could be due to dirt or impurities present in
the cuvettes which are used to fill the sample and hence lead to deviation of
the result.
5. What is the function of every substance used in this suppository preparation? How can the different contents of PEG 1000 and PEG 6000 affect the physical characteristics of the formulation of a suppository and the rate of release of drug from it?
Polyethylene
Glycol (PEG) polymers are water soluble or water miscible type of bases. The PEG used in this experiment is PEG 1000 and PEG 6000.
Numerous active ingredients (example Paracetamol in this experiment) can be
dissolved in PEGs and have a good bioavailability. They act as carrier bases,
solubilisers and absorption improvers for the drugs. PEG such as PEG 1000
and PEG 6000 that is used in this experiment increases the effective dispersion
and delivery of drugs through the rectal route by diffusing out from the PEG as
PEG degrades. The drug will be released by melting within the body and also by
dissolving in the body fluids. By choosing appropriate
combinations of different PEGs, optimum drug release rate from the suppository
is possible, that is, the drug is not too strongly sustained in the carrier
bases and can be easily released. As a result, the rate of absorption through
the rectal mucosa and bioavailability increases.
The Paracetamol that is used in the
preparation of the suppository acts as the active ingredient. It is the main
substance in the drug formulation which has the major role in contributing to
the required drug therapeutic effects in the body.
The desired
solidity can be adjusted by choosing the molecular weight and suitable ratios.
Higher proportions of high molecular weight polymers produce preparations which
release the drug slowly and are also brittle. Less brittle products which
release the drug more readily can be prepared by mixing high polymers with
medium and low polymers. The PEG 1000 give very soft masses while PEG 6000 will
give more solid products. The use of different contents of PEG 1000 and PEG
6000 results in different effects on the physical characteristics of the
suppository produced and this will subsequently affect the rate of drug
released from the suppository. More hydrogen bonds are formed between the PEG
6000 molecules and drug molecules when the more PEG 6000 is used. This will
result in the increase of the hardness of the suppository and also the
difficulty of the drug released from the suppository. The production of
whitish, very hard, less sticky and very rough suppository will be obtained. On
the other hand, PEG 1000 produces whitish, very soft, most sticky, and very
smooth suppository. Thus, suitable and appropriate combination ratio of PEG
1000 and PEG 6000 is important in the production of an optimum drug delivery
with optimum bioavailability of drugs available to the body and also to avoid
too hard or too soft suppository.
CONCLUSION
Different composition of base can affect the physical
characteristic of suppositories. High amount of PEG 6000 will produce hard and
less greasy suppository. However, high amount of PEG 1000 will give soft and
greasier suppository. Proper combination of PEG will give the optimum drug
released rate.
REFERENCES
“Poly(ethylene glycol)”,
http://www.sigmaaldrich.com/catalog/product/aldrich/81260?lang=en®ion=MYretrieved on 10/5/2014.
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