The objective of this
experiment is to study the effect of different composition of base on 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:
Analytical balance Water
bath 37oC
Weighing boats Dialysis
bag
Spatula Glass
rod
50ml and 100ml beaker 5ml
pipette
Hotplate Kuvets
plastics
5ml measuring cylinder Spectrophotometer
UV/Vis
Suppository mould set
Reagents:
Polyethylene glycol (PEG) 1000
Polyethylene glycol (PEG) 6000
Paracetamol
Distilled water
Procedures:
1. Paracetamol saturated stock solution is prepared by
adding 10g of Paracetamol in 5ml distilled water.
2. The 10g suppository is prepared using the formulation
below
Suppository
|
Group
|
PEG 1000
(g)
|
PEG 6000
(g)
|
Paracetamol stock solution
(ml)
|
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
|
3. The suppository is shaped using the suppository
mould. The shape, texture and color of the suppository is observed and
discussed.
4. The suppository is placed in the water bath 10ml at
37oC and the time for the suppository to melt is recorded.
5. The suppository is placed inside the dialysis bag and
placed in the 50ml beaker. The beaker then placed inside the water bath 37oC.
 |
| Diagram 1 |
6. The sample is pipette in 5 minutes interval and the
release of the Paracetamol from the suppository is determined using the
spectrometer UV/Vis. The distilled water must be stirred first before the
sample is taken.
Discussion :
1.
Compare the
physical appearance of the suppository formed.
Suppository
|
Group
|
Shape
|
Hardness
|
Greasiness
|
Colour
|
I
|
1,5
|
Bullet
|
+
|
+
+ + +
|
Intense
white
|
II
|
2,6
|
Bullet
|
++
|
+
+ +
|
Clearly
white
|
III
|
3,7
|
Bullet
|
+++
|
+
+
|
Milky
white
|
IV
|
4,8
|
Bullet
|
++++
|
+
|
Clearly
white
|
All suppositories are bullet-shaped because same type of
mould is used to make the suppositories. From suppositories I to IV, the
content of PEG 1000 decreases while the content of PEG 6000 is increasing. The
hardness of the suppositories increases from I to IV. This is because
increasing the content of PEG 6000 increases the number of hydrogen bonds
between the molecules. Therefore, hardness and strength of suppositories
increases. PEG 6000 less oily and this make the contents of the suppositories
less oily and drier. The surface of suppositories look smooth.
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 of PEG 6000(g)
|
Time for suppositories to
dissolve (min)
|
Average
(min)
|
Average time(min)
|
||||
0
|
Group 1
|
55.14
|
Group 5
|
37.37
|
46.26
|
46.26±8.89
|
|
3
|
Group 2
|
30.00
|
Group 6
|
50.18
|
40.09
|
40.09±10.50
|
|
6
|
Group 3
|
36.46
|
Group 7
|
30.14
|
33.30
|
33.30±3.16
|
|
9
|
Group 4
|
55.47
|
Group 8
|
55.52
|
55.50
|
55.50±0.03
|
|
 |
Polyethylene
glycol is a synthetic polyether that is readily available in a range of
molecular weights.Polyethylene
glycol (PEG) is a water soluble base that has highest water misciblity. PEG
with higher moelcular weight (PEG 6000) will exist in waxy solid form while PEG
with lower molecular weight (PEG 1000) will exsit as greasy semisolid. Thus,
the combinations of these two bases will lead
to the different drug release rate and physiochemical properties.
The
dissolution rate of the suppository and the time taken to melt the suppository
is influenced by the PEG 6000 is the lyophilic base in the suppository
paracetamol .The increase in the content of PEG 6000 in the suppository makes
it to become more insoluble in the water and and required more time to dissolve
in water. The PEG 6000 has the lower tedency to absorb water compared to PEG
1000. Thus, the higher the content of PEG 6000 ,the more difficult the
formulation of suppository to dissolve in the distilled water.
Based on the graph above, it shows
that the time for the suppository to melt decrease gradually as the amount of
PEG 6000 in a suppository formulation increases until 6g of PEG 6000 . However
the dissolving time increase sharply when PEG 6000 9 g is used. Based on the
theory , the result obtained has some error. But, it should be increase in the
dissolving time of suppository in 37 oC distilled water when the
porportion of PEG 6000 in the formulation increase.
The inaccurate of the result may due
to some experimental error. The
temperature in the water baths is not fix at 37oC, higher
temperature may caused the suppository to dissolve faster. The time taken for
the suppositories to solidify in the fridge is not set also which cause the
suppository to not solidy completely when it is put into water bath and each
group put the suppositories in the fridge in different duration It may also
because of different bath of materials being used to make the suppositories..
Besides, the step in making the suppository is also vary among each group, some
group got used levigation method to incorporate and mix drug while some group
mix directly.
3. Plot the graph of UV absorption
against time (Procedure 6). Explain the plotted graph.
 |
In the experiment, the
dialysis bag is used as a membrane for
the release of paracetamol from the suppository. The UV absorption at 520nm is
used to determine the amount of the paracetamol released in the distilled water
from the suppository bases. Theoretically, UV absorption is proportional to the
rate of drug release from the suppository. In other word, the UV absorption
should increases with the increases of the rate of drug release from the
suppository. Thus, the shape of the graph should be in sigmoid curve. Based on
the plotted graph, the value of UV absorption at 520 nm increases when the time
is also increases. In the experiment , there are some errors occurred .The
sample and apparatus used in the experiment might be contaminated with
impurities and this will definitely affect the accuracy of the data obtained.
The other assumption that can be made is the dialysis bag might not be tightly
tied and some of the Paracetamol may leak out. In addition, the temperature of
the water bath that should be 370C is hard to be maintained due to
the surrounding and make the temperature to be lower than 370C.
Furthermore, the distilled water needs to be stirred thoroughly
with the glass rod before the sample is taken for analysis.
The release of Paracetamol for
Suppository is faster at the early stage and becoming slower with time.
Therefore, initially, the graph of the UV absorption should increases
exponentially. As the time increases, the increase in UV absorption will become
lower due to the concentration gradient across the dialysis bag decreases with
time. As the entire drug has released from the suppository into the distilled
water in the beaker, the concentration of the drugs will become constant and
therefore, the UV absorption be constant as well.
4.
Plot a graph of UV absorption versus time for other suppositories that have
different formulation. Compare and discuss the results.
 |
In
this experiment, there are total 4 parameters which are controlled in vitro to
resemble the 4 conditions in vivo in human. The first parameter is temperature.
Throughout the experiment, we use 37 degree Celsius which indicates the body
temperature. However, it may not be true as the body temperature may show some
variations at the different period of time. For instance, during the sleep
time, our body temperature may show the slight reduction due to the minimal
metabolic rate. When this happens, the 37 degree Celsius is the overestimation
of the body temperature. Next, the second parameter is the release medium, in
which the distilled water is being used as it can allow the traverses through
dialysis bag. However, the volume and the composition of the medium is not an ideal solution which can
indicates the condition in the rectal area. The third parameter is the contact
area between the suppository and the medium. In this experiment, we still don’t
have the real apparatus to mimic this parameter ideally in vivo. The last
parameter is the membrane factor. In this experiment, we use the dialysis bag.
However, this membrane may form a resistance for the release of drugs from
inside to the medium.
In
this experiment, theoretically, the suppository which contains the least amount of PEG6000
suppository should release the drugs more easily and rapidly and it is followed
by suppository 2, 3 and 4 which show the gradual increase in the composition of
PEG6000. PEG6000 is has the higher molecular weight compared to PEG1000 and it
increase the hydrogen bond between the molecules in the suppository, causing
the slowest release of the drug from the suppository. However, this experiment
result shows the deviation from what we expect from theory. This may be due to
the errors happened in experiment.
Besides
that, the graph shown for each suppository should have the sigmoid shape, in
which, the drug concentration in the medium should increase with the time
proportionally until it reaches a stage where most of the drug is being released from the dosage form.
However, in this graph, the graphs for the suppository do not show such manner,
especially graph for suppository 2 which shows the great fluctuation in the
progress. Again, it may be due to the experimental errors.
There
are many errors may occurs in the experiment. These errors include
improper method of compounding, causing
non-homogenous dispersion of drugs in
the PEG suppository base and inaccuracy of the UV
spectrometer. Also, the insufficiency in cleaning
of the surface of dialysis bag before the analysis is done. Other errors
that may also contribute to the incorrect results include the inconsistency of
temperature, and delaying in pipetting out the sample.
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?
PEG 1000 and PEG 6000 are the water-soluble
carrier bases. As PED degrades in our body after the rectal administration of
Paracetamol, the drugs melt, diffuse out from PEG and dissolve in the body
fluids. Suitable combinations of different PEGs will allow optimum drug release
rate from the suppository. This means that the drug is not too strongly
sustained in the carrier bases and can be easily released. As a result, rate of
absorption through the rectal mucosa and bioavailability increases.
Paracetamol is the active ingredient
that will exert the therapeutic effects in the body.The use of different contents of PEG
1000 and PEG 6000 results in different effects on the physical characteristics,
subsequently affecting 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. Besides that, the production of dry, hard, smooth, coarse,
tackier and clear white suppository will be obtained.
Hence, it is important to choose the
correct combination ratio of PEG 1000 and PEG 6000 to avoid the production of
extremely hard or soft suppository and to ensure an optimum bioavailability of
the drugs can be obtained.
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.
Reference:
1.
Pharmaceutics:
the science of dosage form design, Aulton, M.E.2002
