TITLE
Assessing the effect of different content material
on the characteristics of a suppository formulation.
OBJECTIVES
To study the effects of cooperating different
composition of bases on the physical characteristics of the suppository formed
and its release rate of drugs.
INTRODUCTION
Suppositories are used
mainly for the administration of drugs via the rectal route and it is generally
consists of vehicle in which the drug is incorporated and in some cases
additives are coformulated. There are two main classes of suppositories
vehicles which are glyceride type fatty bases and the water soluble base. Note
that the viscosity of the molten bases plays an important role in which they
determine the flow into the moulds and also the separation of the drug
particles. During and after melting in the rectal cavity the suppository mass
is forced to spread over the absorbing surface, the rate of which may be
determined partly by its viscosity. A good suppositories base should be
chemically and physically stable during storage as a bulk product, nontoxic,
inert, should have no incompatibilities with drug molecules and should permits
an optimal release of the drug it contains. In this experiment, we used
macrogols type of bases in which it consists of mixtures of polyethylene
glycols (PEG) of different molecular weight eg: PEG 1000 and PEG 6000 and we
also determine the effect of using only single PEG molecular weight on the
suppositories formulation eg: PEG 6000.
Paracetamol is as an antipyretic
and analgesic agent, and is currently available for oral and rectal
administration as different preparations. The rectal suppositories are often
essential for treating febrile children with emesis or the circumstances in which
oral treatment is contraindicated. Previous studies on the antipyretic efficacy
of rectal paracetamol have shown conflicting results. Drugs administered distally by pass the liver, whereas
drugs administered in the proximal part of the rectum are drained into the
portal system and are subject to the hepatic first-pass effect. Polyethylene
Glycol (PEG) was used in the experiment as
it possess many desirable
properties. PEG are chemically stable, nonirritating, miscible with water
and mucous secretions, and can be formulated, either by molding or compression,
in a wide range of hardness and melting point. It does not melt at body temperature,
but dissolve to provide a prolonged release drug. Some polyethylene glycol polymers may be used singly as
suppository bases but, more commonly, formulas call for compounds of two or
more molecular weights mixed in various proportions as needed to yield a
finished product of satisfactory hardness and dissolution time.
APPARATUS
Weighing
balance, weighing boat, spatula, 50ml beaker, 100ml beaker, hotplate, measuring
cylinder, suppository mould, water bath (370C), dialysis bag (10cm),
thread, glass rod, 5ml pipette and a pipette-bulb, plastic cuvette and
spectrophotometer UV/Vis.
MATERIALS
Polyethylene
glycol (PEG) 1000, Polyethylene glycol (PEG) 6000, Paracetamol.
EXPERIMENTAL
METHOD
1. Saturated
solution of Paracetamol stock is prepared (10g in 5ml distilled water).
2. Paracetamol
suppository (10g) is formulated using the formula as below:
Suppository
|
Group
|
Material (g)
|
Paracetamol stock
solution (g)
|
Total (g)
|
|
PEG 1000
|
PEG 6000
|
||||
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
|
3. The
suppository is shaped by using the suppository-mould. The shape, texture, and
colour of the formed suppository is described and compared.
4. One
suppository is put into the beaker containing distilled water (10ml, 370C)
and the time for the suppository melt is recorded.
5. One other
suppository is put into the dialysis bag and both the end of the bed is tied
neatly. The bag then is put into the beaker (100ml) containing distilled water
(50ml) that has been heated to a temperature of 370C.
6. In 5 minutes
interval, an aliquot of the sample is pipette (3-4ml) and the released
Paracetamol from the suppository is determined using the spectrophotometer
UV/Vis. The distilled water is stirred first using a glass rod before taking
the sample.
QUESTION AND DISCUSSION
1. Differentiate the physical characteristics of suppository and give your comment.
Physical characteristics
|
Suppositories
|
|||
I
|
II
|
III
|
IV
|
|
Shape
|
Torpedo
|
Torpedo
|
Torpedo
|
Torpedo
|
Physical state
|
Solid
|
Solid
|
Solid
|
Solid
|
Hardness
|
Hard
|
Hard
|
Hard
|
Very hard
|
Appearance
|
Dull
|
Shiny
|
Dull
|
Dull
|
Colour
|
White
|
White
|
White
|
White
|
The shape of the suppositories produced is according to the shape of the mould.
Torpedo shape of suppositories eases the administration into the rectum.
When the bases, PEG 1000 and PEG 6000 melted and cool down, the mixture
solidified at room temperature.
PEG 1000 is a soft solid whereas PEG 6000 is a hard solid. The hardness depends
on the molecular weight of PEG. The number indicates the average molecular
weight of PEG. Mixing these two PEGs in the formulation with different ratio
will result in different hardness. Using a higher ratio of PEG 6000 to PEG 1000
will result in a harder suppository. Therefore, the hardness of suppository
increases from formulation I to IV.
Most
of the suppositories appear dull. Only suppository II appears shiny on the
surface. All suppositories are white in colour, showing the original colour of
the bases used and also the colour of paracetamol.
2. Plot a graph of the average time taken for the suppository to melt against the amount of PEG 6000 used in the formulation. Compare and discuss the results obtained.
The two bases
that were used in the formulation of the paracetamol suppository prepared in
the experiment are polyethylene glycol (PEG) 1000 and polyethylene glycol (PEG)
6000. The use of different molecular weight of PEG in the formulation is to
attain desired requirements in the production of suppository with different
intended applications. Molecular weight of PEG will affect both the physical
and chemical stability of the suppository. This explains why the suppositories
with different amount of PEG of different molecular weight exhibit different
melting point. Theoretically, as the molecular weight of PEG used increases,
the melting point of the suppository will also increase. This will prolong the
time taken for the suppository formulation to melt.
In the
experiment, the amount of PEG 6000 used varied from 0 g to 9 g. As the amount
of PEG 6000 increases from 0 g to 3 g, the average time taken for the
suppository to melt has shown an increase too. But when the amount of PEG 6000
was further added to 6 g and 9 g, the shorter time needed for the suppository
to melt at 37 degree Celsius. This shows some inaccuracy in the results
obtained and recorded, as we compare to the theoretical readings that were
supposed to be obtained.
3. Plot a graph of UV absorption against time.
Analyse it.
time/ min
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
UV
absorption
|
0.060
|
0.075
|
0.080
|
0.084
|
0.087
|
0.091
|
0.093
|
0.095
|
0.094
|
0.102
|
0.106
|
0.107
|
0.109
|
The
experiment determine the in vitro release of paracetamol suppositories against
time. From the graph of UV absorption against time as shown above, the extent
of drug release was assessed from the total amount of drug present in the
dissolution medium for every 5 minutes interval. The suppository preparations
was used for the assessment of drug release rates. A slope obtained from linear
regression analysis of the plot was determined as the drug release rate
constant. The decrease in drug release at higher surfactant concentration as
obtained is most likely attributable to micellar entrapment of the drug, resulting
in retardation of the drug release. Although the surfactants at optimum
concentration did not improve drug release but they have absorption-promoting
effects so it will be useful if they were incorporated into the suppositories.
The
formulations of the suppositories uses mixture of polyethylene glycol which are
PEG 1000 and PEG 6000 that different in term of melting range. 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 will give more solid products.
By
using UV spectrophotometry, it can measures the rate of in vitro drug release
as a function of time which can reflect either reproducibility of the product
manufacturing process or in limited cases, in vivo drug release. A compound
will exhibit absorption in the UV region if it contains one or more
chromophores such as aromatic nitro, azoxy, nitroso, carbonyl or azo groups.
UV-spectra showed that the drug absorbed appreciably at 254 nm so this
wavelength was selected as the detection wavelength. The calibration curve for
the paracetamol suppository was found to be linear. In the experiment, increasing
drug release can be seen on the graph.
Showing that the rate of drug release is increasing against time.
4 Plot a graph of UV absorption against time for formulation suppository that have different composition. Differentiate and discuss the result.
Y-axis=Average UV absorption value
X-axis=Time (min)
Theoretically, the graph obtained should obey the sigmoid curve. But, all the graph obtained by us does not obey the sigmoid curve. The results obtained shown on the graph are increased and decrease at
several times. The result shows the unusual sigmoid curve.
According to the experimental result obtained, Formulation II suppository has the highest
peak, followed by Formulation I, IV and III. Beer-Lambert Laws states that the higher the absorbtion of UV, the higher the amount of drug in the solution. This means that Formulation II has the highest drug
release rate compared to the other formulations. While the Formulation III has the lowest drug release rate.
Formulation II and I suppository have higher peak than Formulation IV and III. This means Formulation II and I have higher drug release rate compared to Formulation IV and III. Theoretically, the ideal formulation for suppository to have the highest drug release rate is 40% of PEG 1000 and 60% of PEG 6000. So, the ideal formulation used in this experiment should be the formulation III which contain 33.33% of PEG 1000 and 60% of PEG 6000. The higher the percentage the PEG 6000 used, the higher the drug release rate. This is because PEG 6000 will enhance the drug release. But, too high percentage of PEG 6000 will decrease the drug release rate instead of enhance it. Based on the results obtained from experiment, the suppository that shows highest release rate is from Formulation II. This may be due to some experimental errors occur.
Theoretically, formulation I has the lowest drug release rate because the absence of PEG 6000 in the formulation. Although there is PEG 1000 in the formulation, it only has little effect on drug release. PEG
6000 has much more influence on drug release compared to PEG 1000. But the result that we get is contraindicated with the theory.
Although formulation IV has the highest percentage of PEG 6000, it does not show the highest drug release rate. This is because too many PEG 6000 will cause the formation hydrogen bond between PEG and
paracetamol. It requires the longer time to reach the highest value of drug release, as the suppository is the hardest. As a result, the drug release rate decreases.
The inaccurate result that we get from the experiment is due to some error happen when conducting the experiment. Example of errors that happen are uneven stirring of the solution, unstable temperature, mistake in the suppository formation and impurities can all lead to the experimental errors.
5 .What are the functions of each of the materials used in the preparation of the suppositories? How does the different composition of PEG 1000 and PEG 6000 used affect the physical characteristics of a suppository formulation as well as its rate of drug release?
The paracetamol in the preparation of susppositories is the active ingredient. It is used to determine the rate of its release from the dialysis bag, affected by different composition of the suppository bases used. PEG 1000 and PEG 6000 are the water soluble suppository bases which dissolve the Paracetamol and they are able to melt and release the drug at or below body temperature. The drug release for polyethylene glycols base depends on the dissolution rate rather than the melting of the base. The different in PEG 1000 and PEG 6000 is their molecular weight. PEG 6000 has a higher molecular weight than PEG 1000, so it is harder too as compared to PEG 1000 as the hardness of polyglycols increases with increasing molecular weight. Therefore, when different composition of the bases used in the suppository formulation, the physical characteristics as well as the rate of drug release will be affected. The suppository produced will be harder and its rate of drug release will be slowed when more of PEG 6000 was used in the formulation. On the other hand, the suppository will be soft and its drug release rate will be higher when lesser PEG 6000 was used in the formulation. Higher proportions of high molecular weight polymers produce preparations which release the drug slowly and are also brittle. Overall, less brittle products which release the drug more readily can be prepared by mixing high polymers with medium and low polymers.
CONCLUSION
Different compositions of bases affect the physical characteristics of suppository formed and its release rate of drugs.
REFERENCES
1. Aulton, M.E.2002. Pharmaceutics: The Science of Dosage Form Design. Edinburgh: Churchill Livingstone.
2. Pharmaceutics, The Science of Dosage Form Design, Michael Aulton, 3rd.
3. http://www.clariant.com/C125720D002B963C/picklist/C0EB1376B40AC1C9C125726500432C94/$file/Polyethylene_glycols_(PEGs)_and_the_pharmaceutical_industry.pdf
4. http://pharmlabs.unc.edu/labs/suppository/bases.htm
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