Title:
Evaluation of the effect of different formulations on suppository characteristics.
Evaluation of the effect of different formulations on suppository characteristics.
Objectives:
1.
To
study the effect of different composition of bases on the physical
characteristics of suppositories.
2.
To determine the effects of different composition
of bases on the rate of drug release.
Introduction:
Suppository is a solid formulation of different sizes and
shapes suitable for rectal, vaginal or urethral drug administration where it
dissolves or melts and is absorbed into the bloodstream. The
ideal suppository is generally conical
or bullet-shaped and should have all these properties where it must be able to
melt at body temperature, 370C, non irritating, physically and
chemically stable, inert, high viscosity when melted. It should be able to
release the drug locally or systemically. The advantage of suppository is that
it can prevent first pass effect , avoid the digestive enzymes and thus
increase bioavailability. But, suppository have some disadvantages. It can
cause mucosal irritation, patience compliance problems, erratic and undesired
absorption.
The drug needs to be dispersed in suitable suppository bases.
Good bases are non-toxic, do not cause irritation, do not interact with other
drugs and also easy to be mould into a suppository. Different composition of
base will affect the rate and limit of release of the drug from the suppository.
If
a drug is more soluble in base, this will slow down the release rate of drug
from suppository. On the contrary, a drug which is less soluble in base will be
more readily released.
In this experiment, the effects of the different base
composition to the suppository physical characteristics and also to the drug
release characteristics are evaluated. Water-soluble
base, polyethylene glycol is used.
Apparatus:
Analytical
balance, weighing boats, spatula, 50ml and 100ml beaker, hotplate, 5ml
measuring cylinder, suppository mould, water bath 37oC, dialysis
bag, glass rod, 5ml pipette, plastic cuvette, UV spectrophotometer
Materials:
Polyethylene
glycol (PEG) 1000, Polyethylene glycol (PEG) 6000, paracetamol, distilled water,
2 strands of thread
Methods:
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
|
4. 1 suppository is placed into the beaker containing 10ml of saline water at 370C and time required to melt the suppository is recorded.
5.1 suppository is filled into dialysis bag. Two terminal end of the bag is assured to be tied up neatly using thread. The dialysis bag is placed into the 100ml beaker which containing 50ml saline water being heated up to 370C.
6. An aliquot sample with 3-4ml is pipette at 5 minutes interval. The rate of release of paracetamol from the suppository is determined using UV-visible spectrometer. Make sure saline water is stirred by glass rod before sample is taken out.
Results:
1. Compare the physical appearance of the suppository formed.
Suppository
|
Group
|
Material (g)
|
Shape
|
Greasiness
|
Hardness
|
Colour
|
|
PEG 1000
|
PEG 6000
|
||||||
I
|
1,5
|
9
|
0
|
Bullet-shaped
|
Very greasy
|
Very soft
|
White, opaque
|
II
|
2,6
|
6
|
3
|
Bullet-shaped
|
Moderately greasy
|
Soft
|
White, opaque
|
III
|
3,7
|
3
|
6
|
Bullet-shaped
|
Greasy
|
Hard
|
White, slightly transparent
|
IV
|
4,8
|
0
|
9
|
Bullet-shaped
|
Least greasy
|
Very hard
|
White, transparent
|
Discussion:
The shape of all the suppositories
produced by each group are the same which is the bullet-shaped due to the same
shape of the moulds used. This particular shape of suppositories eases the
administration of suppository into the rectum. The difference in the quantity
of PEG 1000 and PEG 6000 used by each group lead to the formation of
suppositories with different physical characteristics.
PEG 1000 is a soft solid whereas
PEG 6000 is a hard solid due to the difference in the molecular weight between
them. The hardness of the suppositories
increases when the amount of PEG 6000 increases. This is because PEG 6000
contains higher content of hydroxyl groups within the structure. More of
intra-molecular and inter-molecular hydrogen bonds are formed between PEG
molecules, thus rendering the overall structure strength. Therefore, using a higher ratio of PEG 6000 to
PEG 1000 will result in a harder suppository. Therefore, the hardness of
suppository increases from formulation of suppository I to IV.
Besides that, suppository I to IV has decreasing greasy
properties due to the decreasing of the composition of PEG 1000. PEG 1000 is
less hydrophilic and has more lipophilic property. Therefore, suppository with
the high content of PEG 1000 will result in the formation of more greasy
suppository. For example, the suppository with formulation I is very
greasy meanwhile for the suppository with formulation IV is the least greasy
and very dry due to the absence of the PEG 1000.
Finally, as for the colour of suppositories, since the active
ingredient that we used is paracetamol which is white in colour, the colour of
the suppositories produce will take on the same white colour too but differ 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 time needed to melt suppository versus amount of PEG
6000 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)
|
56.0
|
61.0
|
58.75
|
52.0
|
27.45
|
31.06
|
48.63
|
56.0
|
Amount of PEG 6000 (g)
|
0
|
3
|
6
|
9
|
Average of time (min) (¯x ± SD)
|
58.5 ±
2.5
|
55.38
± 3.38
|
29.53
± 1.81
|
52.32
± 3.69
|
Discussion:
In this experiment, PEG is used as the suppository base. Two types
of PEG which are PEG 1000 and PEG 6000 are being used in this experiment. A
graph of mean time versus amount of PEG 6000 has been plotted. The suppository
is placed in a beaker containing 10mL distilled water with temperature of 370C
and the time needed to melt the whole suppository is recorded.
PEG 6000 is a suppository base and theoretically, increasing the
mass of the PEG 6000 will make the suppository more solid because the molecular
weight is increased. The presence of hydroxyl (OH) group in the suppository
cause increase in time for the suppository to melt. The higher the amount of
PEG 6000 used, the more the OH group that will be present in the suppository.
Therefore, there will be more hydroxyl group forming hydrogen bond with
paracetamol. With the increase in the formation of hydrogen bond, the
suppository formed will be harder and time needed to completely melt the
suppository will increase in water. This is because time needed for the
dissociation of the hydrogen bond is more difficult with the increase in the
formation of the hydrogen bond. Thus, the time taken for the suppository to
melt should actually increases with the increasing amount of PEG 6000 in the
suppository.
Based
on the graph above, the time needed for the suppository with 0g of PEG 6000 to
melt is supposed to be the shortest. However, the results deviate for the
suppositories that contain 0, 3, 6 g of PEG 6000 g. For this 3 suppositories,
the average time needed decreases with the increasing amount of PEG 6000, with
suppository 0g requiring the longest time to melt. This shows that the results
we obtained is inappropriate and does not comply to the theory. Errors may have
occurred in the procedure of this experiment. Besides that, from the graph, it
can be seen that the average time needed for the suppository with 9g PEG 6000
increases abruptly after the lowest duration of time recorded which was for
suppository with 6g PEG 6000 to melt. The time taken for suppository containing
9g PEG 6000 to melt measured by both Group 4 and Group 8 has a large
difference. The time taken for suppository to melt measured by Group 4 is
shorter while Group 8 is much longer. They are not around the same range.
The
deviation and inaccuracy of the result is majorly affected by the errors occured
while conducting the experiment. Error made during measuring and transferring
the ingredient while making suppository may alter the results. Moreover,
deviation of the temperature of the water bath by different groups where higher
temperature will increase the melting of the suppository, producing the shorter
time needed cause inaccuracy in the results. Another cause may due to some of
the group might stir the beaker containing suppository which make it faster to
dissolve. Hence, these errors have to
be avoided in order to improve the accuracy of the experimental result.
1.
For each 5 minutes, an aliquot sample (3-4mL)
is pipette and determines the release of Paracetamol from the suppository by
the spectrometer UV-visible. Make sure the distilled water is stir with the
glass rod before the sample is taken.
Time (min)
|
UV-visible Absorption
|
||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
|
UV absorption at 520nm
|
0.033
|
0.038
|
0.043
|
0.048
|
0.097
|
0.260
|
0.314
|
Discussion:
Based
on the graph, the rate of release of Paracetamol was slow initially but
increased gradually over time. The reading of UV absorption remain
constant between the 10th to 15th minute. This is due to
the wax that coat the active ingredients was not fully dissolved yet. After the
15th minute, the reading of UV absorption increased
tremendously because the wax coating has dissolved completely and released higher
amounts of active ingredient.
1.
Plot graph of UV absorption against time for
the suppository formulation with different compositions. Discuss and compare
the results.
Discussion:
From the graph above, the results
obtained from the experiment are inaccurate. The readings for the suppository
I,II,III and IV is not increasing gradually which maybe due to experimental
errors described below. Theoretically, all the graphs should be in sigmoid
shape. Suppository may initially dissolve slowly and paracetamol diffuse from
the dialysis bag into water in beaker. Thus, the paracetamol concentration in
water will be increased by time until all paracetamol are released and become
saturated in water, then the paracetamol concentration will be constant.
From
this graph, it shows that different formulation of suppository give rise to
different rate of drug release profile. The releasing rate of paracetomol is
measured by spectrometry. According to theory, suppository IV which contains
the greatest amount of PEG 6000 will give the lowest rate of drug releasing.
This is because the higher amount of hydrogen bonds formed between the base
molecules and the paracetamol molecules. This causes the drug molecules
(paracetamol), to be held stronger in the formulation and thus exert a lower
releasing rate. The reading from the spectrometry should show an increasing
trend but a slowest rate. The drug releasing rate from the suppository I should
be the highest theoretically because it does not consist of PEG 6000. The graph
obtained should be increasing initially and then become constant gradually as
all the drug is released into the water.
However,in the experiment,
suppository I which does not contain PEG 6000 gives a lower paracetamol release
rate compared to other suppositories because presence of PEG 1000 also allow
paracetamol delivery of the suppository into the rectum. Suppository II
contains PEG-6000 that can be used as a drug delivery agent to increase drug
release so it has higher paracetamol release rate compared to suppository I.
The appropriate percentage for PEG suppository is 40% PEG 1000 and 60% PEG
6000. Suppository III shows the most ideal combination whereby percentage of
PEG 1000 is 33.3% and that of PEG 6000 is 66.7%. So, suppository III should
have the highest paracetamol release rate. However, according to the graph from
the experiment, suppository III graph is not the highest according to the
theory. This may due to the technique and experimental error during experiment
as the suppository II graph is not a sigmoid shape. Suppository IV which
contains the highest amount of PEG 6000 will give the lowest paracetamol
release rate. This is due to the higher amount of hydrogen bonds formed between
the PEG base molecules and the paracetamol molecules. This causes the
paracetamol to be held stronger in the suppository formulation, resulting in a
lower releasing rate. The reading for supository IV is ideal since the reading
was slowly increase and highest at 30 minutes of the experiment showing that it
have slower release rate.
The
inaccurate results obtained maybe due to several errors, such as the errors in
the preparation of the suppositories or there is presence of impurities in the
formed suppositories. Besides, the uneven stirring process before the content
of the mixture is pipetted also can contribute to the inaccuracy of the results
which form a few small fluctuations in the line graph. Some precaution steps
should be carried out to obtain an accurate result. The surface of dialysis bag
should be cleaned before immersing it into the distilled water and suppository
should be filled into the bag carefully to prevent breakage of the bag. Mould
of suppository must wait until it become solid and make sure the paracetamol
disperse well in the suppository. Thus, errors must be avoided and special
precautions must be taken to achieve a successful experiment.
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?
There
are three ingredients used in the experiment which are paracetamol,
polyethylene glycol ( PEG) 1000 and polyethylene glycol ( PEG) 6000.
Paracetamol is a drug that is used as the active ingredient for this
suppository. It is an antipyretic and analgesic agent. It is commonly used to
treat fever. PEG 1000 and PEG 6000 are used as base in this suppository and is
medicinally used as laxative for short term relief of constipation. PEG assists
in extended release of drug from the dosage form. PEG is water-soluble polymer,
it can be used to create very high osmotic pressures.
A suitable combination of PEG
allows an optimum drug release, 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
PEG shows high stability and the desired solidity can be adjusted by choosing desired
combinations of PEG. The PEG 1000 and PEG 6000 represent PEG with different
molecular weight. PEG 1000 has smaller molecular weight compared to PEG
6000.
PEG
6000 has decreased solubility in water and solvent, and has higher melting
point compared to PEG 1000. So, the suppository with high proportion of PEG
6000 will dissolve slowly in water. Suppository with high amount of PEG 1000
will dissolve faster in water. The suppository produced from PEG 1000 will tend
to be softer and suppository made from PEG 6000 will be harder. The rate of
drug release from the dialysis bag will be faster when PEG 1000 is used as base
compared to PEG 6000. This is due to less solubility of high molecular
weight of PEG in water. So, the suppository with PEG 6000 that is less
soluble will release the drug content in the suppository slowly in water.
Conclusion：
The suppository composition will affect the physical property and the
drug release rate from the suppository. Different percentage combination of PEG
6000 and PEG 1000 determines the properties of a suppository. The higher the
amount of PEG 6000, the harder the suppository and less soluble in water.
References:
