EXPERIMENT
4: EVALUATION OF THE EFFECT OF DIFFERENT FORMULATION ON SUPPOSITORY
CHARACTERISTICS
OBJECTIVES:
To study the effect of different
composition of base on the physical characteristic of suppositories.
INTRODUCTION:
Suppository
is a medicated solid formulation comes in different sizes and shapes in which
drugs are suitable to be administered to patient in rectum, vagina or urethra.
It is generally conical or bullet in shape. The suppository bases must be able
to melt at body temperature, 370C or dissolve in small amounts of
fluids that are present in rectal area. Therefore, good suppository must be
able to dissolve when being administered into rectal or vagina and release drug
locally or systemically. Bases that are usually used in a formulation is cocoa
butter. The amount of dose of drug incorporated into a suppository depends on
the release properties of the base.
Suppository is taken when a person
unable to take medicine orally and is mainly used to treat constipation. The
advantage of suppository is that it can prevent first pass effect and thus
increase bioavailability. Without the
need of passing through gastrointestinal tract also prevents patient suffering
from gastric irritation. The suppository is mainly used in old people, post
operative people, bed ridden people, in insane people, in infants and kids.
Kids who dislike the bitter taste of medicine can take suppository. If there is
severe nausea or vomiting, it is advisable to use suppository as well.
The action level of suppository
depends on the nature of drug, types of bases, concentration of drugs and
absorption rate of targeted site. pH of the mucosal is important for drug
absorption. Weak acids and bases can be absorbed more effective than strong
acids and bases. This is due to highly ionized drugs are poorly absorbed. Drug
has to be incorporated into a suitable suppository base in order to deliver the
drug efficiently to the targeted site. A different composition of suppository
base will influence the drug release rate. 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. A good base
must not cause toxicity, does not cause irritation, does not react with the drug
and easy to form suppositories. Water-insoluble fats are largely used as
suppository base however in this experiment, water-soluble base, polyethylene
glycol is used. Water soluble base is the choice for quicker drug absorption.
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
- Paracetamol
saturated stock solution was prepared by adding 10g of Paracetamol in 5ml
distilled water.
- The 10g
suppository was prepared using the formulation below:
- The suppository was
shaped using the suppository mould. The shape, texture and color of the
suppository were observed and discussed.
- The suppository was
placed in the water bath 10ml at 37oC and the time for the
suppository to melt was recorded.
- The suppository
was placed inside the dialysis bag and placed in the 50ml beaker. The
beaker was then placed inside the water bath 37oC.
- The sample was pipette in 5 minutes interval and the release of the Paracetamol from the suppository was determined using the spectrometer UV/Vis. The distilled water must be stirred first before the sample is taken.
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
|
Results and Discussion:
1. 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 PEG 1000 and PEG 6000 in the formulation of the suppository will
affect the physical characteristics of suppository. PEG is a suppository base
that is soluble in water. 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
increases with the increasing composition of PEG 6000 from Suppository I to IV.
This means that Suppository IV is the hardest one. This is because there is
more hydrogen bonding formed in this suppository. PEG 6000 also increases the
clarity of the suppository. All the suppositories are in white colour.
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 Suppository
IV, it is less waxy and looks very dry due to the absent of the PEG 1000.
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 required to
dissolve the suppository (minutes)
|
Mean, x
|
Standard Deviation,
SD
|
I
|
1
|
55.14
|
46.26
|
8.89
|
5
|
37.37
|
|||
II
|
2
|
30.00
|
40.09
|
10.50
|
6
|
50.18
|
|||
III
|
3
|
36.46
|
33.30
|
3.16
|
7
|
34.14
|
|||
IV
|
4
|
55.47
|
55.50
|
0.03
|
8
|
55.52
|
Composition of PEG
6000 (g)
|
0
|
3
|
6
|
9
|
Mean of time
(minutes) (X± SD)
|
46.26±8.89
|
40.09±10.50
|
33.30±3.16
|
55.50±0.03
|
Polyethylene glycol (PEG) is a water soluble base that has highest water
misciblity among the water miscible base, absorption base and hydrocarbon base.
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.
Different combinations of these hydrophilic and lypophilic suppository bases
contribute to the different drug release rate, physiochemical properties and
microbiological attack.
PEG 6000 is the lyophilic base in the suppository
paracetamol prepared which will then influence the dissolution rate of the
suppository and also the time taken to melt the suppository as well. The higher
content of PEG 6000 in the suppository makes the it to become more insoluble in
the water and dissolution of paracetamol out of the suppository requires longer
times. Hence, the average time required to melt the suppository becomes longer
too. This is mainly because of the higher molecular weight of PEG 6000 compared
to PEG 1000 makes it to haven lesser possibility to interact with the water
molecule by using the hydrogen bond. The PEG 6000 has the lower possibility to
absorb water compared to PEG 1000. This lead to the suppository with higher PEG
6000 content melts slower 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. However, the dissolving time increases
sharply when PEG 6000 increases from 6g to 9 g is used. Based on the theory on
the above paragraph, the result obtained has some error. Errors occur because
of the temperature in the water bath is not fix at 37oC as it is
difficult to be controlled. The time taken for the suppositories to solidify in
the fridge is not set. This causes some suppositories do not solidify
completely when it is put into water bath. Besides, the steps in making the
suppository are vary among each group, some group used levigation method to
incorporate the bases with paracetamol while some group directly mix the bases
with paracetamol without levigation method, and this causes different
uniformity of suppository. The difference of uniformity between bases and
paracetamol will produce different suppository that may affect the experiment
result.
Hence, several precautions should be taken throughout the
experiment. First, ensure that the beaker containing the sample is always
maintained at even temperature in water bath. Levigation method should be used
to ensure a better distribution between the base and paracetamol, so as to
produce a more uniform content of suppository. These precautions may cut down
the errors formed while conducting experiments.
3. Plot the graph of UV absorption
against time (Procedure 6). Explain the plotted graph.
Time
|
UV absorption
|
||||||||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
|
UV absorption at 520nm
|
0.000
|
0.032
|
0.036
|
0.041
|
0.047
|
0.047
|
0.048
|
0.052
|
0.053
|
0.057
|
0.061
|
0.069
|
0.096
|
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 also increases. However, there is a constant of UV
absorption from 20 to 25 minutes.
The release of Paracetamol for Suppository ΙI 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.
There is a constant value of UV absorption from 20 to 25
minutes. It can be said that the data obtained is slightly inaccurate due to
some errors occurred during the experiment. The sample and apparatus used in
the experiment might be contaminated with impurities and this will definitely
affect the accuracy of the data obtained. In addition, the temperature of the
water bath that should be 370C is difficult to be maintained due to
the surrounding environment and make the temperature to be lower than 370C.
Therefore, several precautions should be taken during the
experiment. The cuvette should be dried completely before inserting into the
absorption spectrophotometer. We should stir the solution containing sample in
the beaker before taking the sample for analysis. Lastly, ensure that the
beaker containing the sample is always maintained at even temperature in water
bath. These precautions may cut down the deviations formed from errors in
conducting experiments.
4.
Plot a graph of UV absorption versus time for other suppositories that have
different formulation. Compare and discuss the results.
In this experiment, different composition of PEG 1000 and 6000 are used in the formulation of suppositories. Polyethylene glycol (PEG) acts as hydrophilic bases in the formulation of suppositories. PEG 1000 has an average molecular weight of about 1000 while PEG has an average molecular weight of about 6000. Different composition will give different results. Based on the graph, there is a wide range of variation which do not correlates with the theoretical principle. Theoretically, suppositories that are prepared with the different combination of PEG 1000 and 6000 show different release rate of drug against the time that contribute to solubility and dissolution of drugs in the aqueous medium.
Hence, the graph obtained for the four different formulations of suppositories should be increasing initially and then become constant gradually as all the drug is released into the water and diffuses out from the hydrophilic matrix with time. And, the suppository with the highest amount of PEG 6000 will show the slowest release rate due to the stronger hydrogen bonds formed with Paracetamol substances which hinders the release of Paracetamol. Decreasing the high molecular weight PEG (6000) concentration and increasing low molecular weight PEG (1000) concentration in the base resulted enhancing the in-vitro release of the drug and vice versa. Water solubility of the drug suppository increases as the molecular weights of PEG decrease due to the water absorbing properties of PEG. Thus, the highest rate of release is expected for suppository I due to the lowest proportion or amount of PEG 6000 in the formulation while formulation suppository IV with higher contents of PEG 6000 will give the slowest releasing rate of drug due to the strong hydrogen bond among molecules PEG 6000 with molecules Paracetamol.
The UV absorption will increase with time until it reaches a plateau stage where the entire drug has been released. However, from the graph obtained, suppository II shows the higher rate of drug release than suppository I which is deviates from the theory. In fact, the suppository II has higher concentration of PEG 6000 and lower concentration of PEG 1000 that should have lesser drug release rate than I. Suppository II shows the higher rate of drug release than suppository III as it has higher composition of PEG 1000 and lower amount of PEG 6000 that slow the release rate of drug. This obeys to the theory.
In this experiment, different composition of PEG 1000 and 6000 are used in the formulation of suppositories. Polyethylene glycol (PEG) acts as hydrophilic bases in the formulation of suppositories. PEG 1000 has an average molecular weight of about 1000 while PEG has an average molecular weight of about 6000. Different composition will give different results. Based on the graph, there is a wide range of variation which do not correlates with the theoretical principle. Theoretically, suppositories that are prepared with the different combination of PEG 1000 and 6000 show different release rate of drug against the time that contribute to solubility and dissolution of drugs in the aqueous medium.
Hence, the graph obtained for the four different formulations of suppositories should be increasing initially and then become constant gradually as all the drug is released into the water and diffuses out from the hydrophilic matrix with time. And, the suppository with the highest amount of PEG 6000 will show the slowest release rate due to the stronger hydrogen bonds formed with Paracetamol substances which hinders the release of Paracetamol. Decreasing the high molecular weight PEG (6000) concentration and increasing low molecular weight PEG (1000) concentration in the base resulted enhancing the in-vitro release of the drug and vice versa. Water solubility of the drug suppository increases as the molecular weights of PEG decrease due to the water absorbing properties of PEG. Thus, the highest rate of release is expected for suppository I due to the lowest proportion or amount of PEG 6000 in the formulation while formulation suppository IV with higher contents of PEG 6000 will give the slowest releasing rate of drug due to the strong hydrogen bond among molecules PEG 6000 with molecules Paracetamol.
The UV absorption will increase with time until it reaches a plateau stage where the entire drug has been released. However, from the graph obtained, suppository II shows the higher rate of drug release than suppository I which is deviates from the theory. In fact, the suppository II has higher concentration of PEG 6000 and lower concentration of PEG 1000 that should have lesser drug release rate than I. Suppository II shows the higher rate of drug release than suppository III as it has higher composition of PEG 1000 and lower amount of PEG 6000 that slow the release rate of drug. This obeys to the theory.
Deviations or inaccuracy occurred in the experiment may
be due to impurities, parallax error, and equipment used give inaccurate readings, uneven temperature of the
water bath and others. Existence of impurities
results from improper cleaning of the cuvette for assay. Cuvettes that are not
properly dried before we insert a new sample for assay may affect the readings.
Dialysis bag that is not tied well before inserting into water bath leads to
the fluctuation readings. Besides, inaccuracy of readings may also caused by
the obtained sample form unstirred solution in beaker before analysis.
Therefore, several precautions should be taken during the
experiment likewise ensuring the cuvette is dried completely before inserting
into the absorption spectrophotometer. We should stir the solution containing
sample in the beaker before taking the sample for analysis. Lastly, ensure that
our beaker containing the sample is always maintained at even temperature in
water bath. These precautions may cut down the deviations formed from errors in
conducting experiments.
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.
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 of suppository, such as 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.
APPENDIX:
Polyethylene glycol
(PEG) 1000 and Polyethylene glycol (PEG) 6000 were being heated
Paracetamol was added
into the molten mixture of PEG 1000 and PEG 6000 and heated
Formation of foam when
paracetamol being added into the molten mixture
Suppositories
formulation was added into the suppository-mould
Suppositories that have
been cooled
One of the
suppositories was added into the dialysis bag
One of the
suppositories was being melted in distilled water at 37⁰C
Different suppositories
from group 1, 2, 3 and 4
Distilled water that
contain the drug was being pipette and was put into a cuvette
The cuvet was then put
into the UV/Vis Spectrophotometer
UV/Vis
Spectrophotometer
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