FACULTY PHARMACY
PHARMACEUTICAL
TECHNOLOGY II
(NFNF 2263)
SEMESTER 2
SESSION 2012/2013
LAB REPORT 4
SUPPOSITORY
NAME :
LIM ANNE YEE (A131494)
LIM GUCCI (A136085)
LIM ZEN HUEI (A136194)
THE THIAN SIANG (A136169)
PUTERI EFFY NASTASHEA BINTI
HOSLAM (A136042)
LECTURER :
DR. NG SHIOW FERN
DATE : 6th MAY 2013
EXPERIMENT 4
Title
Impact Assessment
of Different Ingredients on the Characteristics of a Suppository
Formulation
Objective
To study the effect of using different base composition on
the physical characteristics of a suppository formulation
Introduction
Suppository is a solid formulation with various sizes and
shape which is suitable for rectal administration. A good suppository must melt
down after administration into the rectal and release the drug for localized or
systemic effect.
The drug needs to be dispersed in a suitable suppository
base. A good base should not be toxic, does not produce irritation, does not
react with the drug, and easy to form into a suppository. Different base
composition will affect the rate and release limit of a drug from suppository.
In this experiment, the effect of different base composition
on the physical characteristics of the formed suppositories and its effect on
the release of the drug from it are studied.
Procedure
1. The
paracetamol powder (1g) is weighted and prepared.
2. Paracetamol
suppository (10g) is prepared using the following formula:
Suppository
|
Group
|
Material
|
Solution
of saturated stock Paracetamol (mL)
|
Total
(g)
|
|
PEG
1000
|
PEG
6000
|
||||
1
|
1,5
|
9
|
0
|
1
|
10
|
2
|
2,6
|
6
|
3
|
1
|
10
|
3
|
3,7
|
3
|
6
|
1
|
10
|
4
|
4,8
|
0
|
9
|
1
|
10
|
3. The
suppository is prepared by using suppository-mould. Explain and compare the shape, texture, and
color of the suppository.
4. One
suppository is inserted into the beaker which contains distilled water (10ml, 37 celcius ) and the time taken required to melt
it down is determined.
5. One
suppository is inserted into the dialysis bag and it is ensured that both ends
of the bed are tightly tied. Then, the
bag is inserted into the beaker (100ml) which contains distilled water (50ml)
which is preheated to 37 celcius.
6. At 5 minutes
interval, one aliquot sample (3-4ml) is pipette and the release of Paracetamol
from the suppository is determined by using UV-visible spectrometer. It is
ensured that the distilled water is stirred with glass rod before taking the
sample.
Results and Discussion
1) Compare
the physical characteristics of suppositories that formulated and give comment.
Suppository
|
Group
|
Material (g)
|
Shape
|
Greasiness
|
Hardness
|
Colour
|
|
PEG 1000
|
PEG 6000
|
||||||
I
|
5
|
9
|
0
|
Bullet-shaped
|
Very greasy
|
Soft
|
White
|
II
|
6
|
6
|
3
|
Bullet-shaped
|
Greasy
|
Slightly hard
|
White
|
III
|
7
|
3
|
6
|
Bullet-shaped
|
Slightly greasy
|
Hard
|
White
|
IV
|
8
|
0
|
9
|
Bullet-shaped
|
Least greasy
|
Very hard
|
Transparent
|
Based on the experiment, all the
suppositories have the shape of a bullet since the mould that is being used is
of this shape. The quantities of PEG 1000 and PEG 6000 different for each group
and this will lead to formation of suppositories with different physical
characteristics.
For the formulation
that has the highest amount of PEG 1000, which means that it has the lowest
quantity of PEG 6000 shows the greasiest surface compared to the other
suppositories. As for the formulation with lowest amount of PEG 1000 and
highest in the amount of PEG 6000, the suppository formed is the hardest of
all. The former suppository provide ease to be administered to the patient
compared to the latter one and the latter one may lead to pain in the process
of administering.
In other words, the
higher the quantity of PEG 6000 in a formulation, the less greasy the
suppository will be. As for hardness, we can conclude that the higher quantity
of PEG 1000 (lower quantity of PEG 6000), will produce softer suppository. 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 be white 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 the suppository against the quantity of PEG 6000
in the formulation. Compare and discuss the result.
Amount of PEG 6000 (g)
|
0
|
3
|
6
|
9
|
||||
Group
|
1
|
5
|
2
|
6
|
3
|
7
|
4
|
8
|
Time taken to melt (min)
|
55
|
37
|
30
|
56
|
36
|
30
|
55
|
55
|
Average time (min)
|
46
|
43
|
33
|
55
|
||||
PEG 6000 or also known as Polyethylene
Glycol 6000 has high molecular weight of ethylene oxide and it is a
water-soluble chemical. The amount of PEG 6000 will influence the release in
vivo of the drug in the body because of owing to the solubilizing character of
this base and due to low dielectric constant drugs may tend to remain in the
base and release of acetylsalicylic acid may be slow. Therefore, we can say
that the increasing amount of PEG 6000 will slow down the release of
acetylsalicylic acid. Hence, the graph above shows that the highest amount of
PEG 6000 (9g) need longest time (55mins) to melt the suppository. However, for
the absence of PEG 6000, the time needed to melt the suppository is longer than
the suppository that have immediate amount (3g and 6g) of PEG 6000. This may be
due to the influence of the high amount of PEG1000 inside the suppository.
Besides, there are some errors occurring during the experiment for example during
the making of suppository and also during the process of drug release whereby
the water bath temperature is not constant.
3) Plot the graph of UV absorption against time
(Procedure 6). Give your comments.
UV absorption at 520nm for Group 8 (Suppository IV)
Time (min)
|
UV-visible absorption at 520nm
|
||||||||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
|
UV absorption at 520nm
|
0
|
0.013
|
0.015
|
0.024
|
0.031
|
0.037
|
0.042
|
0.042
|
0.050
|
0.057
|
0.066
|
0.069
|
0.069
|
UV absorption at 520nm for Group 4 (Suppository IV)
Time (min)
|
UV-visible absorption at 520nm
|
||||||||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
|
UV absorption at 520nm
|
0
|
0.013
|
0.015
|
0.024
|
0.031
|
0.037
|
0.042
|
0.042
|
0.050
|
0.057
|
0.066
|
0.069
|
0.069
|
Time (min)
|
Mean UV-visible absorption at 520nm
|
||||||||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
|
UV absorption at 520nm
|
0.000
0.0000
|
0.0175
0.00636
|
0.0205
0.00778
|
0.0255
0.00212
|
0.0300
0.00141
|
0.0340
0.00424
|
0.0365
0.00778
|
0.0375
0.00636
|
0.0440
0.00849
|
0.0510
0.00849
|
0.0590
0.00990
|
0.0625
0.00919
|
0.0655
0.00495
|
According to the
graph plotted based on our result, the release rate of paracetamol is not so proportional
to the time. Theoretically, the graph should be in sigmoid shape which
indicates constant drug release rate until equilibrium is achieved. However,
the graph still showing gradually increase which indicates that the drug is
releasing slowly for PEG 6000 formulation.
At the first 5minutes, 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 may be because of errors that occurred when we conduct
the experiment. 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.
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.
1) Plot a graph of UV absorption vs. time for
other suppositories that have different formulation. Compare and discuss the
results.
From the graph above, the
results obtained from the experiment are not very accurate. Although
suppository I, III and IV are gradually increased, suppository II graph is
fluctuating 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 the Journal of Applied
Pharmaceutical Science, it is stated that “When PEG-6000 was used as a
channeling agent in this formulation drug release was increased accordingly but
higher concentration of PEG-6000 results in decreasing release rate of drug
because of increasing viscosity of the matrix channels”. Therefore, in the
experiment, suppository I which does not contain PEG 6000 will give 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 II graph is slightly higher than suppository III graph.
This may due to the technique and experimental error during experiment as the suppository
II graph is not a sigmoid shape.
Lastly, 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.
Fluctuations and inaccuracy of the results
are obtained from the experiment. This is because some errors may have occurred
in the experiment especially during compounding of suppositories. Paracetamol
powder may be not distributed evenly in the suppository formed. This can lead
to uneven release of paracetamol from the formulation. Uneven stirring process
before the content of the mixture is pipetted also can contribute to the
inaccuracy of the results. Besides, the impurity present in the suppositories
prepared also can contribute to inaccuracy of the results.
1)
What are the functions
of each of the chemicals used in the preparation of suppository? How was the
used of different composition of PEG1000 and PEG6000 affected the physical
characteristics of the suppository and the drug release rate from the
suppository?
Paracetamol
used in the preparation of suppository acts as an active ingredient of the
medication. It is an anti-pyretic agent, and it is also known as a pain-killer.
It is commonly used for the relief of headache and minor pain. It also gives
weak anti-inflammatory activity.
While the Polyethylene glycol used acts as water soluble suppository base, which enable 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. This is because the release rate depends on the hydrophilicity of the suppository base, as it facilitates penetration of the dissolution medium into the base with subsequent wetting and desorption of the embedded drug. The lower the molecular weight of the PEG, the higher the hydrophilicity, as it has higher hydroxyl value as compared to higher molecular weight PEG. In other word, increase amount of PEG1000 enable the suppository to release the drug more rapidly.
While the Polyethylene glycol used acts as water soluble suppository base, which enable 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. This is because the release rate depends on the hydrophilicity of the suppository base, as it facilitates penetration of the dissolution medium into the base with subsequent wetting and desorption of the embedded drug. The lower the molecular weight of the PEG, the higher the hydrophilicity, as it has higher hydroxyl value as compared to higher molecular weight PEG. In other word, increase amount of PEG1000 enable the suppository to release the drug more rapidly.
Conclusion
Different percentage of combination of PEG
1000 and PEG 6000 affects the physical characteristics of the suppository and
the rate of release of the active ingredient.
Reference
1. Rita
Bhatta and Mohammad Salim Hossain, 2011. Evaluation
of Kollidon SR based Ketorolac Tromethamine Loaded Transdermal Film. Journal of
Applied Pharmaceutical Science 01 (08); 2011: 123-127. http://japsonline.com/vol-1_issue-8/23.pdf
2. onlinelibrary.wiley.com/doi/10.1002/jps.2600640706/pdf
