Objectives:
i) To
determine the effect of different composition of base on the physical
characteristics of suppository.
ii) To
determine the effects of different formulations on the drug release from
suppository.
Date of
experiment: 20/5/2015
Introduction:
Suppositories
are solid dosage forms intended for insertion into body orifices (rectum,
vagina, urethra where they melt, soften, or dissolve and exert a local or
systemic effect. Rectal suppositories intended for localized action are most
frequently used to relieve constipation or pain, irritation, itching, and
inflammation associated with hemorrhoids.
An ideal
suppository base should have the following properties:
i) Melts at body temperature or dissolves in
body fluids.
ii) Non-toxic and non-irritant.
iii) Compatible with any medicament.
iv) Releases any medicament readily.
v) Easily moulded and removed from the mould.
vi) Stable to heating above the melting point.
vii) Easy to handle.
ii) Non-toxic and non-irritant.
iii) Compatible with any medicament.
iv) Releases any medicament readily.
v) Easily moulded and removed from the mould.
vi) Stable to heating above the melting point.
vii) Easy to handle.
viii) Stable on storage.
Drugs
should be dispersed in a suitable suppository base. The base must be capable of
melting, softening, or dissolving to release its drug components for
absorption. Different base composition would affect the rate and limit of the
drug released from the suppository.
The
rate at which a drug is released from a suppository and absorbed by the rectal
mucous membrane is directly related to its solubility in the vehicle. When the
drugs are highly soluble in the vehicle, the tendency to leave the vehicle will
be small and so the release rate into the rectal fluid will be low.
The
goal of this experiment is mainly to investigate the effect of different base
composition on the physical characteristics of suppository formed and the
effect of drug release from the suppository.
Apparatus:
Weighing
balance, weighing boat, spatula, 50 ml beaker, 100 ml beaker, hotplate, 5ml
measuring cylinder, suppository mould, water bath (37oC) , dialysis
bag (10cm), thread, glass rod, 5 ml pipette and pipette bulb, Kuvets plastics,
spectrophotometer UV/Vis
Materials:
Polyethylene
glycol (PEG) 1000
Polyethylene glycol (PEG) 6000
Paracetamol
Distilled water
Polyethylene glycol (PEG) 6000
Paracetamol
Distilled water
Procedure:
1.
A saturated paracetamol stock solution is prepared by adding 10g Paracetamol in
5 ml of distilled water.
2.
The 10g Paracetamol suppository is
prepared by using the following formula:
Suppository
|
Group
|
Ingredient
(g)
|
Paracetamol
stock solution (g)
|
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 shaped by using suppository-mould . The shape, texture and
colour of the suppository formed is observed and compared.
4.
The suppository is inserted into a beaker which contain 10ml distilled water
(37oC) and the time that is needed to melt the suppository is
recorded.
5.
A suppository is inserted into a dialysis bag and both ends are tightly tied
with thread. The bag is inserted into a 100ml beaker which contains 50ml
distilled water that has been heated to 37oC.
6.
At each 5 minutes interval, an aliquot sample(3-4ml) is pipetted and the
release of Paracetamol from the suppository is determined by using UV-visible
spectrometer. The distilled water is stirred by using a glass rod before the
sample is taken.
Results:
Results:
Time
(min)
|
UV-visible
absorption at 520 nm
|
||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
|
Group
2
|
0.0200
|
0.0250
|
0.0310
|
0.0340
|
0.0340
|
0.0360
|
0.0360
|
Discussion:
1.
Compare the physical appearance of the suppository formed.
Physical
characteristic
|
Suppositories
|
|||
I
1, 5
|
II
2, 6
|
III
3, 7
|
IV
4, 8
|
|
Shape
|
Bullet shaped, solid
|
Bullet shaped, solid
|
Bullet shaped, solid
|
Bullet shaped, solid
|
Hardness
|
+
|
++
|
+++
|
++++
|
Greasiness
|
++++
|
+++
|
++
|
+
|
Colour
|
White
|
White
|
White
|
White
|
The entire
suppositories produced are of bullet shaped, but the time taken for them to be
solidified varies. This is due to the different composition of PEG1000 and
PEG6000 in the suppositories. Formulation with higher content of PEG1000 will
took longer to be solidified.
PEG 1000 is greasier
and less hydrophilic than PEG6000 which possess more hydroxyl group. Thus the
greasiness of the suppositories increased with the increase of the amount of
PEG1000.
\
\
Besides, the hardness
characteristic of the suppository is increasing from formulation I to
formulation IV with the increasing amount of PEG 6000.
2. Plot a graph of the time needed to melt the
suppository vs. the amount of PEG 6000 in the formulation. Compare and discuss
the results.
Content
PEG 6000 (g)
|
0
|
3
|
6
|
9
|
||||
Time
(min)
|
Group
1
|
65
|
Group
2
|
10
|
Group
3
|
60
|
Group
4
|
74
|
Group
5
|
58
|
Group
6
|
65
|
Group
7
|
43
|
Group
8
|
61
|
|
Average
time ± SD
|
61.5
±
4.95
|
37.5
± 38.89
|
51.5
±12.02
|
67.5
±9.19
|
||||
Based
on the graph shown, we can observe that the time taken for the suppository to
melt is not directly proportional to the PEG 6000 content in gram. The function
of the PEG 6000 content is as a suppository base. As the general knowledge,
increasing the mass of the PEG 6000 will make the suppository more solid. For
that, the time taken for the suppository to melt will be longer as the mass of
the PEG 6000 increase. As shown on the graph above, the time taken for the suppositories
to melt which contain 9g of PEG 6000 is 67.5 minutes which the longest time
among the result. While the shortest time taken for the suppository to melt is
the suppository that contain 3 grams and 6 grams of PEG 6000.
Theoretically,
the time taken for the lowest amount of PEG 6000 should be lowest and vice
versa but the results we obtained is totally inappropriate. The deviation of
the result from the story is majorly effected by the errors occur while conduct
the experiment. Defect of suppository made reduction in mass and will reduce
the time for suppository to dissolve. Error made during measured, and
transferred of the ingredient during making of suppository also may alter the
result. There also possibility that suppository does not solid enough when we removed
it from the mould. 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.
3.
Plot the graph of UV absorption against time (Step 6). Explain the plotted
graph.
Initially, there is small amount of paracetamol detected at 0 time. This is an error that occurs due to inappropriate filling of paracetamol into the dialysis bag.
In this experiment, paracetamol needs to pass through the dialysis bag before it can reach distilled water. Dialysis bag represents human biological membrane while the distilled water represents human blood plasma. The melting process,drug release and drug absorption processes occur in water bath at 37ºC, which represents human body temperature.
At the first 10 minutes, amount of paracetamol released into water in beaker shoots up. This is because there is a great difference in concentration gradient between water in beaker and suppository in dialysis bag. Therefore, paracetamol diffuses out quickly.
This graph deviates from the theory (sigmoid curve). Firstly, 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 on spectrophotometer UV/Vis.
4.
Plot the graph of UV absorption versus time for the suppository formulation
which has different composition. Compare and discuss the result.
Group/
Time (min)
|
UV
absorption at 520 nm (X ± SD)
|
|||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
||
S
U
P
P
O
S
I
T
O
R
Y
|
1
|
0.0130
|
0.1970
|
0.2870
|
0.2080
|
0.2110
|
0.2260
|
0.2970
|
5
|
0.0013
|
0.0045
|
0.0074
|
0.0068
|
0.0082
|
0.0112
|
0.0110
|
|
Average
(X ± SD)
|
0.0072
± 0.0083
|
0.1008
±
0.1361
|
0.1472
±
0.1977
|
0.1074
±
0.1423
|
0.1096
±
0.1434
|
0.1106
±
0.1519
|
0.1540
±
0.2022
|
|
2
|
0.0200
|
0.0250
|
0.0310
|
0.0340
|
0.0340
|
0.0360
|
0.0360
|
|
6
|
0.0000
|
0.0012
|
0.0140
|
0.0110
|
0.0120
|
0.0110
|
0.0160
|
|
Average
(X ± SD)
|
0.0100
±
0.0141
|
0.0131
±
0.0168
|
0.0225
±
0.0120
|
0.0225
±
0.0163
|
0.0230
±
0.0156
|
0.0235
±
0.0177
|
0.0260
±
0.0141
|
|
3
|
0.0020
|
0.0030
|
0.0040
|
0.0070
|
0.0210
|
0.0130
|
0.0190
|
|
7
|
0.0200
|
0.0330
|
0.0300
|
0.0100
|
0.0230
|
0.0130
|
0.0130
|
|
Average
(X ± SD)
|
0.1010
±
0.1400
|
0.0180
±
0.0212
|
0.0170
±
0.0184
|
0.0085
±
0.0021
|
0.0220
±
0.0014
|
0.0130
±
0
|
0.0160
±
0.0042
|
|
4
|
0.0000
|
0.0020
|
0.0030
|
0.0030
|
0.0040
|
0.0040
|
0.0050
|
|
8
|
0.0100
|
0.0180
|
0.0780
|
0.0330
|
0.0460
|
0.0440
|
0.0460
|
|
Average (X ± SD)
|
0.0050
±
0.0071
|
0.0100
±
0.0113
|
0.0405
±
0.0530
|
0.0180
±
0.0212
|
0.0250
±
0.0297
|
0.0240
±
0.0283
|
0.0255
±
0.0290
|
|
From
the graph above, it seems that there are fluctuations on the UV absorption
readings from the UV-visible spectrometer on all four types of suppository
samples analysed in this experiment.
There are 4 parameters of an in
vitro suppository drug release: Temperature, contact area, release medium,
and membranes.
The first parameter is temperature.
In the whole set of experiment, we are using 37oC as the body
temperature for the tests of drug release from suppositories. Although for most
practical purposes they can be set at 37oC but that is not always
the reality. As the body temperature may have slight variations at different
periods of time, for example, during sleep time, when our metabolism rate is
minimal, the temperature may slightly decrease. At this point, measurements of
drug release at 37oC may become an overestimation due to differences
in melting range of the suppository. Also, comparing bases at 37oC
may cause such erroneous conclusions, as what we can see above. We should be
aware that the temperature at which testing is performed is crucial, especially
when aging has occurred.
We shall also consider the release
medium that is used in this test. We could consider the release medium in this
test as the distilled water, which traverses through the dialysis bag, once it
is immersed into the beaker of distilled water. But we need to realize 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.
Another problem is due to the
membrane factor. The ‘membrane’ that 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. We do need to consider that, the membrane may form a
resistance to passing drug molecules, and that the actual release may be
underestimated, although there are stands saying that membrane signifies the
rectal mucosa.
Taking back a look on the experiment
results, theoretically all four suppositories should obtain a graph of
increasing values, only to be varied is the degree of the increase and the
values. Suppository I which contain the least PEG 6000 base should have meet
the conditions for an optimum drug release, yet much to our disappointment, the
results are not in line with our theory.
The results produced by Suppository
II could meet with our theory, i.e. the suppository which contains PEG 6000 and
PEG1000 as the base could release the drug in a short period of time, and
amount of drug release is increasing and keep constant after 15-20 minutes
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?
Paracetamol used in the preparation of suppository is the
active ingredient. Polyethylene glycol used acts as water soluble
suppository base. It enables the
suppository to dissolve in rectal solution and release the medication easily.
Combining PEG of different molecular weights in different ratio provides some control over the consistency, the drug release rate as well as the solidity/hardness of the suppository.
Increasing in the amount of PEG6000 over PEG1000 make the suppository becomes harder, but decrease the drug release rate.
PEG1000 has higher hydrophilicity compared to PEG6000. The drug release rate depends on the hydrophilicity whereby higher hydrophilicity give better drug release rate.
Combining PEG of different molecular weights in different ratio provides some control over the consistency, the drug release rate as well as the solidity/hardness of the suppository.
Increasing in the amount of PEG6000 over PEG1000 make the suppository becomes harder, but decrease the drug release rate.
PEG1000 has higher hydrophilicity compared to PEG6000. The drug release rate depends on the hydrophilicity whereby higher hydrophilicity give better drug release rate.
Conclusion:
The
different amount of combination of PEG 1000 and PEG 6000 in the suppository
preparation affects the physical and chemical characteristics of suppositories
such as the rate of drug release, greasiness texture, and shape of the
suppository.
References:
