TITLE:
Evaluation of The Effect of Different Formulation on Suppository Characteristics
DATE OF EXPERIMENT:
20th MAY 2015
OBJECTIVES:
To study the effect of different composition of base on the
physical characteristic of suppositories.
INTRODUCTION:
Suppository is a solid formulation of
different sizes and shapes suitable for rectal drug administration. Good
suppository will melt after the rectal administration and release the drug
either topically or systematically.
The drug needs to be dispersed in suitable
suppository bases. 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
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 beaker
Hotplate
5ml measuring cylinder
Suppository mould set
Water bath 37oC
Dialysis bag
Glass rod
5ml pipette
Kuvets plastics
Spectrophotometer UV/Vis
REAGENTS:
Polyethylene glycol (PEG) 1000
Polyethylene glycol (PEG) 6000
Paracetamol
Distilled water
EXPERIMENTAL PROCEDURE:
- Paracetamol saturated stock solution is prepared by adding 10g of Paracetamol in 5ml distilled water.
- 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
|
- The
suppository is shaped using the suppository mould. The shape, texture and
color of the suppository is observed and discussed.
- The
suppository is placed in the water bath 10ml at 37oC and the
time for the suppository to melt is recorded.
- The suppository is placed inside the dialysis bag and placed in the 50ml beaker. The beaker then placed inside the water bath 37oC.
- 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.
Results:
|
Time
(min)
|
UV absorption at 520nm
|
|||||||
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
||
|
Suppository
|
I
|
0.013
|
0.197
|
0.287
|
0.208
|
0.211
|
0.226
|
0.297
|
|
II
|
0.020
|
0.025
|
0.031
|
0.034
|
0.034
|
0.036
|
0.036
|
|
|
III
|
0.002
|
0.003
|
0.004
|
0.007
|
0.021
|
0.013
|
0.019
|
|
|
IV
|
0.000
|
0.002
|
0.003
|
0.003
|
0.004
|
0.004
|
0.005
|
|
|
V
|
0.0013
|
0.0045
|
0.0074
|
0.0068
|
0.0082
|
0.011
|
0.011
|
|
|
VI
|
0.000
|
0.0012
|
0.014
|
0.011
|
0.012
|
0.011
|
0.016
|
|
|
VII
|
0.020
|
0.033
|
0.030
|
0.010
|
0.023
|
0.013
|
0.013
|
|
|
VIII
|
0.010
|
0.018
|
0.078
|
0.033
|
0.046
|
0.044
|
0.046
|
|
|
Time (min)
|
Average UV absorption at 520nm ( x ± SD)
|
|||||||
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
||
|
Suppository
|
I
|
0.007±0.008
|
0.100±0.136
|
0.147±0.183
|
0.107±0.142
|
0.110±0.143
|
0.119±0.152
|
0.154±0.202
|
|
II
|
0.010±0.010
|
0.013±0.017
|
0.023±0.012
|
0.023±0.016
|
0.023±0.016
|
0.024±0.018
|
0.026±0.014
|
|
|
III
|
0.011±0.013
|
0.018±0.021
|
0.004±0.027
|
0.009±0.002
|
0.022±0.001
|
0.013±0.000
|
0.016±0.000
|
|
|
IV
|
0.005±0.007
|
0.010±0.011
|
0.041±0.053
|
0.018±0.021
|
0.025±0.030
|
0.024±0.028
|
0.026±0.029
|
|
Discussion:
- Compare and discuss 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
|
Different
composition of the PEG 1000 and PEG 6000 in the formulation of the suppository
will affect the physical characteristic of suppository. PEG is a suppository
base that soluble in water but is rarely use now due to its hydrophilic effect.
It can retain drug and affect the rate
of release of drug. PEG 1000 is less hydrophilic compare to PEG 6000 because
PEG 6000 contain of more hydroxyl group (-OH).
Hardness is
increasing with the increasing of composition of PEG 6000 from the Suppository
I to IV. This shows that Suppository IV is the hardest one. Because there is
more hydrogen bonding formed in this suppository. PEG 6000 also increasing the
clarity of the suppository, all the suppositories are in white color
Besides that,
Suppository I to IV have decreasing waxy 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
composition will make the suppository more waxy as like the Suppository I.
While for the Suppository IV, it is less waxy and looks very dry due to the
absent of the PEG 1000. Moreover, PEG 6000 also increasing the clarity of the
suppository. All the suppositories show white in colour.
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.
|
Suppository
|
Group
|
Time needed to melt the suppository
|
|
I
|
1
|
65 minutes
|
|
II
|
2
|
10 minutes
|
|
III
|
3
|
60 minutes
|
|
IV
|
4
|
74 minutes
|
|
I
|
5
|
58 minutes
|
|
II
|
6
|
65 minutes
|
|
III
|
7
|
43 minutes
|
|
IV
|
8
|
61 minutes
|
|
Amount of PEG 6000
|
0
|
3
|
6
|
9
|
|
Time average (min) (x ± SD)
|
61.5 ± 4.95
|
37.5 ± 38.89
|
51.5 ±12.02
|
67.5 ±9.19
|
Generally, we know that the time required to
melt a suppository is increased with the increased amount of PEG 6000 added. The
time needed to melt the suppository is increasing with amount of PEG 6000 added
because a high composition of PEG 6000 contribute to more of hydroxyl groups
(-OH) that are capable to form strong hydrogen bonds between molecules of PEG
6000 and paracetamol. Therefore, longer time is needed to break the bond in order for the
suppository to melt and release the drug.
But, there is a result deviate from theory which
occurred durring the IV suppository. This may mainly due to the experimental errors. The errors might be our
failure to control the temperature of water bath, weighing error or time
measured error.
3.
Plot graph of UV absorption against time. Give
explanation.
Suppository
with the formula IV
|
Time (min)
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
|
UV absorption at 520nm
|
0.010
|
0.018
|
0.078
|
0.033
|
0.046
|
0.044
|
0.046
|
Y-axis=UV absorption value
X-axis=time (min)
The graph shows the UV absorption
of suppository IV against time. According to the theory, the UV absorption of
suppository generally shall increase as time passes, and the data obtained
shall lead to the plot of a sigmoid-shaped graph. However in our group doing
suppository with formulation IV, the UV reading of the drug is increasing
slowly with a small amount then increase drastically at 5th minutes and
followed by decrease as well as increase after 15th minutes.
Errors may be occur during the preparing the
suppository procedures. Paracetamol molecules may be not disturbed evenly in
the suppository formed. This can lead to the uneven releasing of paracetamol
from the formulation to occur. Besides that, water from the water bath may be
mixed into the mixture in the beaker and thus decrease the UV absorption. Other
than that, it may be our fault when we are taking the sample without mixing the
water surrounding the suppository. This causes the amount of paracetamol amount
in each time sample taken is a large difference and thus affect the UV
absorption.
3. Plot
graph of UV absorption against time for the suppository formulation with
different compositions. Discuss and compare the results.
|
Time (min)
|
Average UV absorption at 520nm ( x ± SD)
|
|||||||
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
||
|
Suppository
|
I
|
0.007±0.008
|
0.100±0.136
|
0.147±0.183
|
0.107±0.142
|
0.110±0.143
|
0.119±0.152
|
0.154±0.202
|
|
II
|
0.010±0.010
|
0.013±0.017
|
0.023±0.012
|
0.023±0.016
|
0.023±0.016
|
0.024±0.018
|
0.026±0.014
|
|
|
III
|
0.011±0.013
|
0.018±0.021
|
0.004±0.027
|
0.009±0.002
|
0.022±0.001
|
0.013±0.000
|
0.016±0.000
|
|
|
IV
|
0.005±0.007
|
0.010±0.011
|
0.041±0.053
|
0.018±0.021
|
0.025±0.030
|
0.024±0.028
|
0.026±0.029
|
|
The graph obtained shows that
suppository with formulation I and IV obey the sigmoid curve except the suppository
with the formulation II and III. This is because there is a high value of UV
absorption at the beginning and then decrease drastically and increase again.
This shows the unusual sigmoid curve.
Formulation
I suppository has the highest peak since it contains the least amount of PEG
6000 means that it has the highest rate
of drug release compared to others formulation type.
Formulation
II and III has 3 and 6 g PEG 6000, thus suppose suppository with formulation II
has higher rate of drug release compared to III which has higher amount of PEG
6000 when time increase. And the graph obtained was actually go according to
the theory.
Formulation IV
contains the highest amount of PEG 6000 among others, it should have slowest
releasing degree of the drug, but in the experiment, it has the second highest
drug release after formulation I (given as the UV absorption), suppose the
curve obtained is flat at the beginning then increase very slowly, it should
require the longest time to reach the highest value of drug release, as the
suppository is the hardest.
These
can only be explained by taking into account the errors that might occur in the
experiment. Uneven stirring of the solution, unstable temperature, mistake in
the suppository formation, impurities can all lead to the experimental errors.
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 polyethylene glycols which are polymers of ethylene oxide and
water and the numerical indicates the molecular weight of the substance. They act as water-miscible base carrier for
active ingredient. Paracetamol is the active ingredient in this experiment.
The different amount of PEG 1000 and PEG
6000 used can influence the physical characteristic and the release rate of
drug from suppository base. Higher amount of PEG 6000 increase hardness of
suppository formed due to stronger hydrogen bond formed between molecules. Due
to this strong hydrogen bonding, the drug release rate will be lowered. Using
higher amount of PEG 1000 will result in softer suppository. This is due to
weaker hydrogen bond formed between the molecules. Lipophilicity of PEG 1000 is
higher thus result in greasier suppository. Drug release will be faster because
the bond formed is weaker.
Different
characteristic of suppositories can be formed by varying amount and molecular
weight of PEG used. Therefore by varying the combinations of PEG, we can obtain
desired consistency and characteristic of suppositories. A balance of
lipophilicity and hydrophilicity of suppository base can be achieved by this
combination. Thus, bases that fulfill desired characteristics can be used in
formulation and this will lead desired rate release of drug from the
suppository base.
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.
REFERENCES:
1. Pharmaceutical Practice.(1996). Diana
M.Collett Micheal E.Aulton.Pulished by Churchill Livingstone.
2. David Troy. 2000. Remington: The Science and
Practice of Pharmacy. Lippincott
Williams & Wilkins. 21th edition. Page 1079-1080
3. http://www.pharmaceutics.comoj.com/PDF/Suppositories_PHR308.pdf
