EXPERIMENT 4 : SUPPOSITORY
TITLE: Evaluation of the
effects of different composition of substance on the characteristics
of suppository formulation.
DATE OF EXPERIMENT: 6
MAY 2013
OBJECTIVE: To
study the effects of different base composition on the physical characteristics of
suppositories formed and on the release of drug from the suppository formulation.
INTRODUCTION:
Suppositories
are solid dosage forms intended for insertion into body orifices (rectum,
vagina, urethra) where they melt, soften, or dissolve and exert a local or
systemic effect. The properties of an ideal suppository base are:
- Melts at body temperature or dissolves
in body fluids.
- Non-toxic and non-irritant.
- Compatible with any medicament.
- Releases any medicament readily.
- Easily moulded and removed from the
mould.
- Stable to heating above the melting
point.
- Easy to handle.
- Stable on storage.
In
this experiment, water-miscible base, that is polyethylene glycol (PEG) or also
called macrogol is used. 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.
Polyethylene
glycol is non-toxic, odorless, neutral, lubricating, nonvolatile and
nonirritating and is used in a variety of pharmaceuticals and in medications as
a solven, dispensing agent, ointment and suppository bases, vehicle, and tablet
excipient.
Weighing
machine Water
bath (37oC)
Spatula 1
dialysis bag (10 cm)
1
weighing boat 2
strand of thread
1
beaker 50 ml 1
glass rod
1
beaker 100ml 1
set of pipet (5ml) and pipet bulb
1
measuring cylinder 5 ml 1
plastic cuvette
1
set suppository mould Spectrophotometer
UV
Polyethylene
glycol (PEG) 1000
Polyethylene
glycol (PEG) 6000
1. 1g
of Paracetamol powder is weighed.
2. Paracetamol
Suppository 10g is prepared using the formulation below:
Suppository
|
Group
|
|
Paracetamol
(1g)
|
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 mould by using suppository-mould
provided. The shape, texture, and colour of all the suppositories are compared
and verified.
4. One
of the suppositories is inserted into a beaker containing distilled water
(10ml, 37oC) and the time taken required for it to melt is recorded.
5. One
of the suppositories is inserted into a dialysis bag and both end of the bag is
tightly tied as shown in the figure below.
The dialysis bag is placed into a beaker (100ml) containing a distilled
water (50ml) heated at 37oC.
6.
Every 5 minutes interval, a small amount
of sample (3-4 ml) is pipetted and the rate of diffusion of Paracetamol from
the suppository is determined by using a spectrometer UV-visible. Before taking
the sample, the distilled water is stirred with a glass rod.
Time taken (min)
|
Absorbance of
UV-visible
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
Absorbance of UV on 520 nm
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Compare
and explain on the physical appearance of the suppository formed.
Criteria
Group
|
Group 1
(PEG 1000:6000
= 9:0)
|
Group 2
(PEG 1000:6000
= 6:3)
|
Group 3
(PEG 1000:6000
= 3:6)
|
Group 4
(PEG 1000:6000
= 0:9)
|
Texture
|
Smooth but less shinning
|
Smooth and shinning
|
Smooth and shinning
|
Smooth and shinning
|
Shape
|
Bullet-shaped
|
Bullet-shaped
|
Bullet-shaped
|
Bullet-shaped
|
Colour
|
White and opaque
|
White
|
White
|
Clear white
|
Hardness
|
A little soft and less brittle
|
Hard and brittle
|
Hard and brittle
|
Hard solid and and brittle
|
Greasiness
|
Very greasy
|
Greasy
|
Slightly Greasy
|
Least greasy
|
Poly
ethylene glycols (PEGs) are family of water-soluble linear polymers formed by
the additional reaction of ethylene oxide (EO) with mono ethylene glycols (MEG)
or diethylene glycol. Polyethylene glycols are available in average molecular
weight ranging from 200 to 8000 and in this experiment, polyethylene glycol
with molecular weight of 1000 and 6000 were used. Polyethylene glycol is
non-toxic, odorless, neutral, lubricating, nonvolatile and nonirritating and is
mainly used as solvent, water soluble, binder, lubricant, plasticizer and use
in ointment base, tablet coating, gelatine capsule, liquid oral medications.
Basically
all the suppositories formed are shinning and smooth and are bullet-shaped. All
the suppositories formed are white in colour but for Group 1, it is opaque
whereas for group 4, the suppositories formed are clear white. This is due to
increasing amount of PEG 6000 and decreasing amount of PEG 1000 used. The
colour of PEG 1000 is white paste which is opaque and the colour of PEG 6000 is
white flake, which is slightly clear.
The
hardness of PEGs increases with increasing molecular weight. Group 4
suppositories are hard due to the use of 100% PEG 6000 and Group 1
suppositories are a little soft because of 100% PEG 1000 used. Besides that, those
with molecular weights of 600-1000 are semisolids. Higher proportions of high
molecular weight polymers produces 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. Degree of
greasiness decreases as amount of PEG 1000 used decreases and amount of PEG
6000 increases this is because those having average molecular weights of
greater than 1000 are wax-like.
QUESTION 2
Plot the graph of time needed to
melt the suppository versus the amount of PEG 6000 in the formulation. Compare
and discuss the result.
PEG 6000 ( g ) content
|
0
|
3
|
6
|
9
|
Time ( min )
|
Group 1 : 55min 14s
|
Group 2 : 30min
|
Group 3 : 36min 46s
|
Group 4 : 55min 47s
|
Group 5 : 37min 37s
|
Group 6 : 56min 18s
|
Group 7 : 30min 14s
|
Group 8 : 55min 52s
|
Average Time ( min )
(x ± SD)
|
46.43±12.46
|
43.15±18.6
|
33.5±4.26
|
55.83±0.06
|
The graph shows the average time required to
melt the suppository against the amount of PEG 6000 used in the formulation.
The polyethylene glycol PEG acts as the suppository base in the formulation. Two different PEGs are used in the
formulation, PEG 1000 and PEG 6000. Since the molecular weight of the PEG 6000
is greater than PEG 1000, formulation with a higher PEG 6000 content will be
more solid and harder. Theoretically, higher PEG 6000 content (with greater
molecular weight) in the suppository has higher meting point and lower
dissolution rate. This is because the stronger bonding within the suppository
leads to lesser interaction of the base with the surrounding water molecule.
Thus, longer time should be required to melt the suppository with greater
amount of PEG 6000.
However, the results obtained from the
experiment were not compatible to the theory. Based on the graph plotted,
suppository with 6g of PEG 6000 recorded the shortest time to melt with average
of 33.5 minutes whereas suppository with 9g of PEG 6000 charted the longest
time required, with 55.82 minutes. There is a decrease in the time required
form 0g to 6g content of the PEG 6000 content. The different in the result may
be due to the large standard deviation calculated and is believed to be
resulted from some errors that had been done in the experiment.
The suppository produced may contain
different amount of the base and the active ingredient from the stated amount
in the table due to the improper procedure and technique. Error in the
measuring and transferring process may decrease the mass of suppositories
produced and thus less time required for melting. The suppository may also be damaged when it
was taken out from the mould. Insufficient solidification of the suppository
may cause the internal structure remained liquefied and make it easier to
dissolve when the outer layer had dissolved in the water. Also, different
technique used by different groups such as stirring can increase the rate of dissolution
of the suppository.
Generally, melting point of PEG is above of
the body
temperature. When
it is administrated via the rectal route, it can dissolve and disperse the medication slowly,
providing a sustained effect in the body.
QUESTION
3
Plot the graph of UV absorption
versus time. Give explaination.
|
Time (min)
|
UV-Visible
Absorption at 520 nm
|
|
0
|
0.000
|
5
|
0.039
|
10
|
0.043
|
15
|
0.046
|
20
|
0.049
|
25
|
0.051
|
30
|
0.063
|
35
|
0.077
|
40
|
0.085
|
45
|
0.084
|
50
|
0.098
|
55
|
0.107
|
60
|
0.124
|
The graph above shows the UV absorption at 520nm for suppository 3 which
contain 3g of PEG 1000 and 6g of Peg 6000. We can observe that the graph fluctuates
(up and downs) as time goes by. Theoretically, the graph should show a
sigmoidal shape. This is because the suppository will dissolve slowly and the
drugs are released slowly at body temperature. So that, the
concentration of drugs in the water is increases with time until all the drugs are
released and the concentration of
drug inside the dialysis bag is equal to the concentration of drug in the
distilled water (isotonic). Once the equilibrium is reached, there is no
movement of drug and the graph will become
constant.
From
the graph obtained, the graph are keep on increasing of UV absorption with time
except at the time of 45minutes there shows a little bit drop of the value.
This slightly deviates from the theory. The error may due to some errors that
occur during the experiment. For example, the solution is not stirred well
before taking solution to investigate and this will affect the result obtained.
This may also due to the accidentally pouring of the distilled water in the
beaker and this can cause the changed in the concentration of the drug.
Plot the graph of UV
absorption versus time for the suppository formulation which have different
composition. Compare and discuss the result.
Time
|
UV absorption average at 520nm (x ± SD)
|
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
suppository
|
I
|
0
|
0.022
|
0.023
|
0.024
|
0.0255
|
0.0265
|
0.0295
|
0.0385
|
0.040
|
0.0435
|
0.0465
|
0.056
|
0.06
|
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
|
0
|
0.0127
|
0.0141
|
0.0156
|
0.0148
|
0.0148
|
0.0177
|
0.0219
|
0.0212
|
0.0205
|
0.0233
|
0.0226
|
0.0184
|
II
|
0
|
0.0575
|
0.0295
|
0.0365
|
0.0350
|
0.0535
|
0.0530
|
0.0625
|
0.072
|
0.07
|
0.0815
|
0.079
|
0.107
|
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
|
0
|
0.03606
|
0.00919
|
0.00636
|
0.01697
|
0.00919
|
0.00707
|
0.01485
|
0.02687
|
0.01838
|
0.02899
|
0.01414
|
0.01556
|
III
|
0
|
0.0305
|
0.034
|
0.036
|
0.038
|
0.0445
|
0.0525
|
0.06
|
0.066
|
0.067
|
0.0745
|
0.0815
|
0.0935
|
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
|
0
|
0.01202
|
0.01273
|
0.01414
|
0.01556
|
0.01485
|
0.01202
|
0.024
|
0.0269
|
0.024
|
0.0332
|
0.0361
|
0.0431
|
IV
|
0
|
0.0175
|
0.0205
|
0.0255
|
0.03
|
0.034
|
0.0365
|
0.0375
|
0.044
|
0.051
|
0.059
|
0.0625
|
0.0655
|
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
±
|
|
0
|
0.00636
|
0.00778
|
0.00212
|
0.00141
|
0.00424
|
0.00778
|
0.0064
|
0.0085
|
0.0085
|
0.0099
|
0.0092
|
0.0050
|
In this experiment, the graph shows a wide range of
variation which do not follow the theoretical principle. The error is occurred
because of the presence of the impurities, parallax error, and equipment used
give inaccurate readings, uneven temperature of the water bath and others. Besides that, the distilled water is not properly stirred before sample
is collected is also among the reason .Different
composition will give different results.
Theoretically the suppository with the highest amount of
PEG 6000 will have the slowest release rate due to the stronger hydrogen bonds
(intermolecular forces) formed with Paracetamol which will hinder the release
of Paracetamol. Suppository I should has
the highest rate of release because of
the lowest proportion or amount of PEG 6000 in the formulation. In the general, the rate of drug release which
can be determine for the UV absorption show a gradual increase until a certain
point where the drugs release will become constant. , and this applies to all the suppository formulation.
QUESTION 5
What are the functions of each ingredients used in the formulation of
suppositories. And how the use of different amount of PEG 1000 and PEG 6000
will affect the physical characteristics of the formulation of suppositories
and rate of release of the drug?
Polyethylene glycol also known as macrogols and act as base. PEG
1000 and PEG 6000,means Polyethylene glycol have different molecular weight of
each polymers. These PEGs can be blended
together to produce suppository bases with varying melting points,
dissolution rates and physical characterisics. Suppositories of varying melting
point and solubility characteristics can be prepared by adding different amount
of PEG 1000 and PEG 6000. While, Paracetamol acts as active ingredient in the
formulation of suppositories.
In our formulation, we
are using 3g of PEG 1000 and 6g PEG 6000. The hardness of PEGs
increases with increasing molecular weight. So when we compared the hardness of
our suppositories of with other group, our suppositories are more hard and
brittle compared with other group which use 9g of PEG 1000 and 0 g of PEG 6000 which their suppositories
are more soft and less brittle. It is means that, our suppositories(3g of PEG
1000 and 6g PEG 6000) have higher melting point and low solubility.
Suppositories are formulated to melt at body temperature and releases drug for effect.
Drug release depends on
the base dissolving rather than melting. Higher proportions of high molecular
weight polymers produce preparations which release the drug slowly and are also
brittle. Melting point above body temperature cause the base disslove in the
body and disperse the medication slowly, providing a sustained effect.
CONCLUSION:
At the end of the
experiment, we are able to investigate the effects of different base
composition onto the physical characteristics of the the suppositories formed
and also the effect of release of the drug from the formulation.
1. Increasing the amount of PEG 6000 and decreasing the amount of PEG 1000
will result in increased shining and hardness, decreased greasiness and
producing clear, white and less opaque suppositories.
2. The highest the amount of PEG 6000 in the suppository formulation, the
highest its melting point and longest the time required for melting. It can be
affected by other factors in vivo such as body temperature and anatomical and
physiological factors of the rectum mucosa.
3. The drug is released slowly from the suppository with increasing time at
the body temperature until equilibrium is reached.
4. Higher melting point and
low solubility of suppository cause the
release of active ingredient from the formulation much slower.