TITLE:
Assessment of the Effects of Different Compositions of
Ingredients Used on the Characteristics of an Emulsion Formulation
OBJECTIVE:
To study the effect of different composition of bases
on the physical characteristics of suppository formed and the effect of the
drug release from it.
INTRODUCTION:
Suppository is a solid formulation with various sizes
and shapes suitable with the rectal administration. A good suppository must
melt after administration into the rectum and release the drug for local or
systemic effect.
Drug
must be distributed homogenously in suitable suppository bases. Good bases are
nontoxic, non-irritant, not interact with the drug and easily formed into
suppository. Different composition of bases will affect the rate and limit of
the release of the drug from the suppository.
APPARATUS:
Weighing balance, weighing boat, spatula, beaker 50ml,
beaker 100ml, hotplate, measuring cylinder 5ml, suppository mould, water bath
(37oC), dialysis bag (10 cm), thread, glass rod, pipette 5ml and
pipette bulb, plastic cuvette, UV spectrophotometer
MATERIALS:
Polyethylene glycol (PEG) 1000, polyethylene glycol
(PEG) 6000, paracetamol
PROCEDURES:
1. A saturated
stock solution of paracetamol is prepared by adding 10g of te paracetamol into
5ml of distilled water.
2. 10g paracetamol
suppository is prepared using the following formula
SUPPOSITORY
|
INGREDIENTS
(g)
|
STOCK
SOLUTION OF PARACETAMOL (ml)
|
TOTAL (g)
|
|
PEG 1000
|
PEG 6000
|
|||
I
|
9
|
0
|
1
|
10
|
II
|
6
|
3
|
1
|
10
|
III
|
3
|
6
|
1
|
10
|
IV
|
0
|
9
|
1
|
10
|
Figure 1: The bases are put on the hotplate to let it melt
Figure 2: The molten bases is poured into the mould
3. A suppository is formed using suppository mould. The shape, texture, and colour of the suppository.
4. One suppository is put in a beaker containing distilled water (10ml, 37oC) and the time for melt is set.
5. One suppository is put into dialysis bag and both ends of the bag is tied with two pieces of thread.
6. At 5 minutes
interval, 3-4ml of sample is pipette and the release of paracetamol from
suppository is determined using the UV spectrophotometer. The distilled water
is stirred with glass rod before taking the sample.
RESULTS AND DISCUSSIONS:
1)
Compare the shape, texture and colour of
the suppository produced.
GROUP
|
SHAPE
|
GREASINESS
|
HARDNESS
|
COLOUR
|
1
|
Bullet-shaped
|
Very greasy
|
Slightly soft
|
white
|
2
|
Bullet-shaped
|
Less greasy
|
hard
|
white
|
3
|
Bullet-shaped
|
Less greasy
|
hard
|
white
|
4
|
Bullet-shaped
|
Less greasy
|
Very hard
|
colourless
|
5
|
Bullet-shaped
|
Very greasy
|
soft
|
white
|
6
|
Bullet-shaped
|
greasy
|
Slightly hard
|
white
|
7
|
Bullet-shaped
|
Slightly greasy
|
hard
|
white
|
8
|
Bullet-shaped
|
Less greasy
|
Very hard
|
colourless
|
Group 1
Group 2
Group 6
Group 7
Different amount of polyethylene glycol
(PEG) 1000 and PEG 6000 results in different physical characteristic of
suppository as stated in the table above. The numbers that are included in the names of
PEGs indicate their average molecular weights. Those with the
higher molecular weights that are more than 1000 are wax like, white solids. For group 1 and 5
from the table, PEG 6000 is not added as base. Thus it gives more greasiness
and reduces hardness to the suppository. The high amount of PEG 1000 causes the
suppository to be in softer form since the boiling point and the molecular
weight is quite low.
Meanwhile
for group 4 and 8, PEG 1000 is not added to the suppository base. It results in
less greasiness, colorless and hard structure of the suppository. This is
because of the high amount of the PEG 6000, which is 9g from the total 10g of
the suppository. Since the molecular weight and the boiling point of the PEG is
high, it gives hardness to the suppository.
2) Plotted a graph
of time needed to melt suppository versus amount of PEG 6000 in the
formulation. Compare and discuss the result.
QUANTITY
OF PEG 6000 USED (g)
|
0
|
3
|
6
|
9
|
TIME
AVERAGE (min) (mean ± SD)
|
66.67 ± 4.78
|
35.095 ± 1.375
|
38.175 ± 1.035
|
63.67 ± 10.33
|
Based on all of the data being collected in this experiment,
we can see that the time taken to melt for each suppositories with different
quantity of PEG 6000 used in the formulation is different. Polyethylene glycol (PEG) polymers is a water
soluble/water miscible bases used in suppository formulation. It consisted of
ethylene oxide and water that are prepared in various length of chain,
molecular weights and physical status. The examples of PEG are PEG 200, 400,
1000, 3350, 6000. These numbers refer to the average molecular weight. Those
with the higher molecular weight s that are more than 1000 are wax like, white
solids with an increase in the molecular weight. Solid polyglycols are
preferred bases as suppository masses. Numerous actives can be dissolved in
PEGs and have then a good bioavailability. The dissipation of the active takes
place not only by melting within the body but also by dissolving in the body
fluids. Usually, various combination of these PEG is used to prepare a good
formulation of suppositories with desired properties. e. The desired solidity
can be adjusted by choosing the molecular weight and suitable ratios. For
example 25% PEG 1000 and 75% PEG 1500 give very soft masses, 25% PEG 4000 S and
75% PEG 6000 S will give more solid products.
From the plotted graph, we can see that the formulation with
the no PEG takes the longest time to melt, followed by the formulation with 9g
PEG, then 6g PEG, and lastly the shortest time taken to melt is the formulation
containing 3g of PEG.
3)
Plot a graph of UV absorption against time. Explain.
Time
|
UV-Visible Absorption
|
||||||||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
|
UV Absorption at 520nm
|
0.005
|
0.023
|
0.036
|
0.039
|
0.050
|
0.055
|
0.070
|
0.063
|
0.072
|
0.094
|
0.121
|
0.131
|
0.156
|
In
this experiment, the suppository is put into a dialysis bag and immersed in a
37oC water bath. The release of paracetamol from the suppository
into the water is determined by the UV absorption. The paracetamol in the water
sample that leaked from the dialysis bag will absorb ultraviolet radiation of
520nm. Thus, the intensity of UV absorption is directly proportional to the
concentration of paracetamol present in the water sample. This meant that the
UV absorption reading is higher when more paracetamol is released from the
dialysis bag. From this graph, it showed the increased in UV absorption for 1
hour. This meant that the paracetamol is released slowly for 1 hour from the
dialysis bag. Besides that, from the graph, we also can determine the rate of
release of paracetamol from the dialysis bag into the water which is the
gradient of the graph.
At
time 0, the solution surrounding the dialysis bag is tested for the UV
absorption. Theoretically, there should be no UV absorption as the diffusion
has not occurred where there is no paracetamol in the solution. The UV
absorption may be due to the delayed sample taking when the diffusion occurred.
This allowed some paracetamol diffused out from the dialysis bag and present in
the solution.
The
37oC water bath modified the body temperature where the suppository
will melt and the drug will be released. This temperature help in the
dissolution of the suppository and drug diffuse out of the dialysis bag
membrane. Polyethylene glycol is soluble in water. As water diffuses into the
dialysis bag, the PEG dissolves and releases the drug.
The
rate of release as indicated by the gradient of the curve (not steep) is almost
constant throughout the experiment with some fluctuations. This may be due to
the errors that occurred during the experiment. The solution is not stirred
before the solution sample is taken. The solution is isotonic to the
suppository within the dialysis bag. Therefore, there is no net diffusion
between the two phases. This is ideal as the release of drug into the solution
is dependent on the concentration of drug in equilibrium with the surrounding.
This will provides a controlled release of drug when it is administered in the
human body. In vivo, the drug released will be absorbed into the body
continuously and constant rate of release of drug can be achieved.
4)
Plot a graph of UV absorption vs. time for other suppositories that have
different formulation. Compare and discuss the results.
Time (min)
|
Absorption of
UV-visible
|
||||||||||||||
 |
GROUP
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
|
I
|
1
|
0.005
|
0.023
|
0.036
|
0.039
|
0.05
|
0.055
|
0.07
|
0.063
|
0.072
|
0.094
|
0.121
|
0.131
|
0.156
|
|
5
|
0.003
|
0.008
|
0.017
|
0.026
|
0.032
|
0.037
|
0.041
|
0.048
|
0.049
|
0.05
|
0.055
|
0. 070
|
0.229
|
||
Mean
|
0.004
|
0.0155
|
0.0265
|
0.0325
|
0.041
|
0.046
|
0.0555
|
0.0555
|
0.0605
|
0.072
|
0.088
|
0.1005
|
0.1925
|
||
SD
|
0.0014
|
0.0106
|
0.0134
|
0.0092
|
0.0127
|
0.0127
|
0.0205
|
0.0106
|
0.0163
|
0.0311
|
0.0467
|
0.0431
|
0.0516
|
||
II
|
2
|
0.02
|
0.022
|
0.032
|
0.023
|
0.04
|
0.028
|
0.045
|
0.068
|
0.052
|
0.147
|
0.074
|
0.076
|
0.069
|
|
6
|
0.004
|
0.04
|
0.037
|
0.055
|
0.055
|
0.063
|
0.074
|
0.085
|
0.079
|
0.109
|
0.096
|
0.109
|
0.111
|
||
Mean
|
0.012
|
0.031
|
0.0345
|
0.039
|
0.0475
|
0.0455
|
0.0595
|
0.0765
|
0.0655
|
0.128
|
0.085
|
0.0925
|
0.09
|
||
SD
|
0.0113
|
0.0127
|
0.0035
|
0.0226
|
0.0106
|
0.0247
|
0.0205
|
0.0120
|
0.0191
|
0.0269
|
0.0156
|
0.0233
|
0.0297
|
||
III
|
3
|
0.017
|
0.024
|
0.025
|
0.029
|
0.033
|
0.036
|
0.04
|
0.045
|
0.059
|
0.079
|
0.081
|
0.086
|
0.09
|
|
7
|
0.029
|
0.055
|
0.081
|
0.1
|
0.108
|
0.115
|
0.129
|
0.143
|
0.164
|
0.179
|
0.186
|
0.175
|
0.293
|
||
Mean
|
0.023
|
0.0395
|
0.053
|
0.0645
|
0.0705
|
0.0755
|
0.0845
|
0.094
|
0.1115
|
0.129
|
0.1335
|
0.1305
|
0.1915
|
||
SD
|
0.0085
|
0.0219
|
0.0396
|
0.0502
|
0.0530
|
0.0559
|
0.0629
|
0.0693
|
0.0742
|
0.0707
|
0.0742
|
0.0629
|
0.1435
|
||
IV
|
4
|
0
|
0.002
|
0.001
|
0.003
|
0.004
|
0.004
|
0.009
|
0.052
|
0.014
|
0.007
|
0.007
|
0.016
|
0.052
|
|
8
|
0.007
|
0.042
|
0.015
|
0.019
|
0.018
|
0.019
|
0.026
|
0.029
|
0.051
|
0.048
|
0.07
|
0.079
|
0.008
|
||
Mean
|
0.0035
|
0.022
|
0.008
|
0.011
|
0.011
|
0.0115
|
0.0175
|
0.0405
|
0.0325
|
0.0275
|
0.0385
|
0.0475
|
0.03
|
||
SD
|
0.0049
|
0.0283
|
0.0099
|
0.0113
|
0.0099
|
0.0106
|
0.0120
|
0.0163
|
0.0262
|
0.0290
|
0.0445
|
0.0445
|
0.0311
|
||
The
graph shows the UV absorption versus time for different composition of
suppositories formulation. The UV spectrophotometry is used wide in the
quantitative analysis of the active substances in the dissolution test. The
different composition of polyethylene glycol (PEG) which is used as a dispersing agent and as a water
soluble base in the formulation of suppositories affects the dissolution rate
or the release of drug from the dosage form. After the sample is subjected to
the dissolution test, aliquot portions of the dissolution medium are withdrawn
at 5 minutes intervals of time and drug uptake is assayed at 520 nm using a
UV-visible spectrophotometer. This test is conducted to assess the amount of
drug release from the suppositories of different composition of bases.
The
release profile from different suppositories formulations are shown in the
graph. Average cumulative drug releases from PEG of suppositories of
formulation I, II, III and IV were found to be 0.1925, 0.09, 0.1915, and 0.03
respectively at the end of 60 minutes. The in vitro drug release data was
subjected to goodness of fit test by linear regression analysis, according to
zero and first-order kinetic equations to ascertain the mechanism of drug
release. The release from most of the formulations was found to follow
first-order kinetics. The graph plotted seems does not really follow the
first-order kinetic. This might be some errors during the test was carried out.
For overall, it is found that, the suppository II (6 g of PEG 1000 and 3 g of
PEG 6000) and suppository III (3 g of PEG 1000 and 6 g of PEG 6000) have the
highest value of UV absorption compare to the suppository I (9 g of PEG 1000
only) and IV (9 g of PEG 6000 only). This means that the rate of release of
drug from suppositories II and III is higher than suppositories I and IV.
Whereas, the rate of release of drug from suppository I is higher than
suppository IV according to the graph above as PEG 1000 in suppository I is
more water soluble than PEG 6000 in suppository IV.
It
was found that the release of paracetamol from suppositories affected by PEG.
This might be due to the fact that a suppository with high composition of PEG
1000 over PEG 6000 is more hydrophilic than the suppository with higher
composition of PEG 6000 over PEG 1000. This is because in terms of release, an
advantage of the shorter chain length PEG types (1000) over the longer chain
length PEG types (6000) was observed for the polymer blends. The polymer
miscibility increased with decreasing chain length due to a decrease in the
Gibbs free energy of mixing. So, it enhances the release of active
substances from the polymer.
5) What
is the function for each ingredients used in the preparation of suppository?
How the use of PEG 1000 and PEG 6000 contents influence the different physical
characteristics as well as a suppository formulation of a drug release from it?
The ingredients used in
the preparation of the suppositories are polyethylene glycol 1000, polyethylene
glycol 6000 and paracetamol. Paracetamol is the active ingredient of the
suppositories and it has analgesic and antipyretic effect. Therefore, it can be
used to relieve pain and to treat fever. Paracetamol is a polar molecule and
sparingly soluble in water.
Macrogols is the nonproprietary name for
polyethylene glycols (PEGs). PEG has been used as laxatives to treat
constipation. It also used in as excipients in pharmaceutical products where
lower molecular weight variants are used as solvents in oral liquids and soft
capsules. Solid variants are used as ointment bases, tablet bindings, film
coatings and lubricants. PEG is a water-miscible base hence it is a hydrophilic
compound. It is washable and a stable compound. In this experiment, PEG was used
as the base for the suppositories.
Polyethylene
glycols are polymers of ethylene oxide and water, prepared to various chain
lengths, molecular weights, and physical states. The numerical designations
refer to the average molecular weights of each of the polymers. Polyethylene
glycols (PEGs) having average molecular weights of 300, 400, and 600 are clear,
colorless liquids, while those with molecular weights of 600-1000 are
semisolids. Those having average molecular weights of greater than 1000 are wax-like,
white solids with the hardness increasing with an increase in the molecular
weight. Therefore, suppositories made with only PEG 6000 will be the hardest
and more brittle compared to suppositories mixed with PEG 1000. Suppositories
made of purely PEG 1000 are almost semi-solid in its appearance and they are
not brittle when pressed.
These
polyethylene glycols can be blended together to produce suppository bases with
varying: melting points, dissolution rates and physical characteristics. Drug
release depends on the base dissolving rather than melting. The melting point
is often around 50°C, hence instead of melting in the rectum, the bases
dissolve slowly (the rate depending on the proportions of PEGs). Higher
proportions of high molecular weight polymer (such as PEG 6000) 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.
Conclusion:
Different
composition of base can affect the physical characteristic of suppositories.
Besides that, the rate of the drug release from the different composition of
suppository is different.
References:
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