4. SUPPOSITORY

TITLE: Evaluation of the effect of different formulation on suppository characteristics.
AIM: To study the effect of different composition of base on the physical characteristic of suppositories.
INTRODUCTION:
A suppository is a drug delivery system that is inserted into the rectum (rectal suppository), vagina (vaginal suppository) or urethra (urethral suppository), where it dissolves or melts and is absorbed into the blood stream. They are used to deliver both systemically and locally acting medications. Suppositories are medicated, solid bodies of various sizes and shapes suitable for introduction into body cavities through rectal administration. Good suppository will melt after the rectal administration and release the drug either topically or systematically.
The medicament is incorporated into a base such as PEG which slowly dissolves in the mucous secretions. The ideal suppository base should be non-toxic, non-irritating, inert, compatible with medicaments, and easily formed by compression or moulding. Different composition of bases 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 beakers
Hotplate
5ml measuring cylinder
Suppository mould set
Water bath 37oC
Dialysis bag
Thread
Glass rod
5ml pipette and pipette bulb
Plastic cuvette
UV spectrophotometer

MATERIAL

Polyethylene glycol (PEG) 1000
Polyethylene glycol (PEG) 6000
Paracetamol
Distilled water
Liquid paraffin

PROCEDURE

1. 10g of suppository is prepared using the formulation below:
Suppository
Group
PEG 1000
(g)
PEG 6000
(g)
Paracetamol (g)
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








2. The suppository is moulded using the suppository mould. The shape, texture and colour of the suppository is observed and discussed.










3. One suppository is placed into a beaker containing 10ml of distilled water (10ml, 37˚C ) and the time required for the suppository to melt is recorded.



4. One suppository is inserted into a dialysis bag and both ends are tied neatly, as shown in the figure below. It is then placed into a beaker containing 50mL of distilled water which is then placed inside the water bath at 37oC.



5. The sample is pipetted (3- 4mL) in 5 minutes interval and the release of Paracetamol from the suppository is determined using the UV-visible spectrometer. The distilled water must be stirred first before the sample is taken.




RESULTS AND DISCUSSION


1. Compare the physical appearances of suppositories formed and give comments.

FORMULATION
GROUP
SHAPE
TEXTURE
COLOUR
I
1
Torpedo
Smooth, hard, oily
Even white
5
Torpedo
Smooth, hard, oily
Even white
II
2
Torpedo
Smooth, hard
Even white
6
Torpedo
Smooth, hard
Even white
III
3
Torpedo
Smooth, hard
Uneven white
7
Torpedo
Smooth, hard, sticky
Milky white
IV
4
Torpedo
Smooth, hard, oily
Uneven white
8
Torpedo
Smooth, hard
Uneven white

The table above shows the comparison between the physical appearances of suppositories in those formulations based on the different quantities of PEG 1000 and PEG 6000 in the suppository base mixtures for each group. Based on the result obtained, the shapes of all the formulation of suppositories are the same shape which are torpedo-shape since that all the suppositories were prepared in the same suppository mould. 
For the texture, formulation with the highest amount of PEG 1000, which means that it has the lowest quantity of PEG 6000 shows the greasiest surface and smooth compared to the other suppositories. Meanwhile, for the formulation with the lowest amount of PEG 1000 and the highest amount of PEG 6000, the suppository formed is the hardest and least greasy. This could be explained, as the physicochemical characters of PEG 6000 forms more strong and stable hydrogen bonds in the suppository compared to PEG 1000. PEG 6000 which has higher molecular weight compare to PEG 1000 has a lot of hydroxyl groups which can form numerous hydrogen bonds between the molecules of the PEG 6000 and the molecules of Paracetamol. Therefore, we can conclude that the higher the amount of PEG 6000, the hardness of the suppositories also will increase.
Then, for the colours of all suppositories are white as the active ingredient used is paracetamol which has white in colour. The intensity of these suppositories are undistinguishable where there are no effect on the colour intensity of the suppository since the colour obtained from all formulation is the same even with different quantities of the PEG 1000 and PEG 6000 but the differences is 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 the time required to melt the suppository against PEG 6000 content in the formulation. Compare and discuss the result.

Amount of PEG 6000 (g)

0

3

6

9
Groups
1
5
2
6
3
7
4
8
Time (min)
(x ± SD)
31
54
27
27
40
50
73
65
42.5 ± 16.26

27 ± 0
45 ± 7.07
69 ± 5.66


























Based on the graph above, it is shown that the time required to melt suppositories are varies in each formulation that contain different amount of Polyethylene glycol (PEG) 6000. PEG 6000 is a suppository base that is 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. Thus, PEG 6000 can make the suppository more solid.

Polyethylene glycol suppositories do not melt at body temperature but rather dissolve slowly in the body’s fluids. Therefore, the base need not be formulated to melt at body temperature. Thus, it is possible, in fact routine, to prepare suppositories from polyethylene glycol mixtures having melting points considerably higher than body temperature. This property permits a slower release of the medication from the base once the suppository has been inserted, and permits convenient storage of these suppositories without need for refrigeration and without danger of their softening excessively in warm weather.

Furthermore, their solid nature permits slow insertion without fear that they will melt in the fingertips (as cocoa butter suppositories sometimes do). Because they do not melt at body temperature but mix with mucous secretions upon dissolution, polyethylene glycol–based suppositories do not leak from the orifice, as do many cocoa butter–based suppositories. Polyethylene glycol suppositories that do not contain at least 20% water should be dipped in water just before use to avoid irritation of the mucous membranes after insertion. This procedure prevents moisture being drawn from the tissues after insertion and the stinging sensation.

Theoretically, the time required to melt suppositories are increases gradually as the amount of PEG 6000 increases. This is because high content of PEG 6000 will make the suppository become harder and solidify. Thus, it will take time to melt when inserted into distilled water (37ºC). Suppository with 9g of PEG 6000 has longer time to melt compared to other suppositories. However, in this experiment, there were a slight error has occurred as we can see on the suppository with 0g of PEG 6000. The time required for it to melt is longer compared to suppository with 3g of PEG 6000. There might be some errors that occurred when conducting the experiment. The possibilities of errors might be due to wrongly measured the amount of PEG 6000. Moreover, the temperature of the water bath may be not fixed at 37ºC which can cause the result not accurate.

3.  Plot a graph UV absorption against time. Give explaination.


Time (min)
UV-Visible Absoption at 520nm
0
0.015
5
0.038
10
0.089
15
0.093
20
0.113
25
0.101
30
0.107
35
0.141
40
0.125
45
0.100
50
0.136
55
0.118
60
0.103























The graph above shows the UV absorption at 520nm for suppository 1 that contains 9g of PEG 1000 and 1g of Paracetamol. This graph shows fluctuates which the line goes up and down. The graph should give a sigmoidal shape as the suppository will dissolve and release slowly at body temperature, 37˚C. The drugs released will increased the concentration of drugs in the water until the concentration reached equilibrium or isotonic as the concentration of the drugs in the dialysis bag same to the concentration of drugs in the water. When the equilibrium achieved the graph should be constant because there is no net movement of drugs.
From this graph, it keep going increase until it drop at 25th minutes. Then the graph elevated again until the 35th minutes and then drop at the 40th to 45th minutes before it strongly increase at 50th minutes and back to fall down at the 55th and 60th minutes. This graph shows big deviates from the theoretical principle which due to many errors may occurred. The errors may occurred due to the presence of impurities during prepare the suppositories, parallax error, the dialysis bag not been tied correctly and also due to the distilled water not stirred properly before collect the sample to measured the UV visible absorption. These errors will affect the results obtained.


4. Plot a graph of UV absorption for different composition of suppository formulations against time. Compare and explain the results.

Time
(mins)
Average UV absorption at 520 nm
0
5
10
15
20
25
30
35
40
45
50
55
60

I
0.015
0.020
0.044
0.024
0.024
0.017
0.018
0.019
0.020
0.019
0.021
0.029
0.025
II
0.015
0.147
0.081
0.167
0.077
0.059
0.048
0.071
0.066
0.107
0.088
0.085
0.077
III
0.039
0.044
0.053
0.057
0.061
0.065
0.070
0.072
0.075
0.078
0.073
0.072
0.082
IV
0.010
0.016
0.026
0.031
0.034
0.024
0.037

0.041
0.043
0.045
0.045
0.050
0.050












Different suppository base compositions will have different effects on the drug release rate over time. In this experiment, we varied the ratio amount of PEG 1000 and PEG 6000 in each of the suppository.  Suppository I has the highest amount of PEG 1000 and none PEG 6000. According to the theory, it should be showing the highest drug releasing rate as well as the UV absorption. This is due to lesser hydroxyl group present in PEG 1000. Thus, there are less strong hydrogen bond formed between the molecules of PEG 1000 and molecules of paracetamol. Little energy would be needed to break the bonds to release the drug. Hence, higher releasing rate is expected and it would cause the UV absorption to be higher. So, from suppository I to suppository IV, the average IV absorbance should increase all the time following this order as the amount of PEG 1000 decreasing while amount of PEG 6000 increasing in this order.
Suppository IV has more hydrogen bonding formed between the molecules of PEG 6000 as it has more hydroxyl groups present in it and the molecules of the paracetamol when they are mix together and formed a suppository. It has the highest molecular weight and this would cause a lower drug releasing rate. Therefore, a longer time and higher energy is needed in order to break down the strong hydrogen bond and subsequently release the drug. This will further lower the UV absorption. Apart from that, suppository II and suppository III has intermediate UV absorption. Suppository III has lower UV absorption than Suppository II as Suppository II has higher PEG 1000 but lower PEG 6000 than Suppository III. Thus, there are less hydrogen bond formed between the Suppository II bases and paracetamol. Less energy would be needed to break the bonds to release the drug. Hence, it would have a higher releasing rate than Suppository III and this would cause the UV absorption of Suppository II to be higher than Suppository III.
            Based on the graph, we can see that Suppository III has the highest UV absorption, while, Suppository IV has lowest UV absorption rate, which indicates that it has lowest drug releasing rate. This did not comply with the actual theory. Besides that, the graph showed deviated much in comparison between results of each two groups. It is due to many errors arisen in the experiment. These errors can be due to the improper method of compounding, non-homogenous dispersion of Paracetamol in the PEG suppository base, inaccuracy of the UV spectrometer, and so on. Other errors that may occur include inconsistency in temperature which may affect the drug release from the suppository, the sample in the beaker did not stir well before pipette out from the solution or could be due to dirt or impurities present in the cuvettes which are used to fill the sample and hence lead to deviation of the result.


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?

Polyethylene Glycol (PEG) polymers are water soluble or water miscible type of bases. The PEG used in this experiment is PEG 1000 and PEG 6000. Numerous active ingredients (example Paracetamol in this experiment) can be dissolved in PEGs and have a good bioavailability. They act as carrier bases, solubilisers and absorption improvers for the drugs. PEG such as PEG 1000 and PEG 6000 that is used in this experiment increases the effective dispersion and delivery of drugs through the rectal route by diffusing out from the PEG as PEG degrades. The drug will be released by melting within the body and also by dissolving in the body fluids. By choosing appropriate combinations of different PEGs, optimum drug release rate from the suppository is possible, that is, the drug is not too strongly sustained in the carrier bases and can be easily released. As a result, the rate of absorption through the rectal mucosa and bioavailability increases.
  The Paracetamol that is used in the preparation of the suppository acts as the active ingredient. It is the main substance in the drug formulation which has the major role in contributing to the required drug therapeutic effects in the body.
The desired solidity can be adjusted by choosing the molecular weight and suitable ratios. Higher proportions of high molecular weight polymers produce 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. The PEG 1000 give very soft masses while PEG 6000 will give more solid products. The use of different contents of PEG 1000 and PEG 6000 results in different effects on the physical characteristics of the suppository produced and this will subsequently affect the rate of drug released from the suppository. More hydrogen bonds are formed between the PEG 6000 molecules and drug molecules when the more PEG 6000 is used. This will result in the increase of the hardness of the suppository and also the difficulty of the drug released from the suppository. The production of whitish, very hard, less sticky and very rough suppository will be obtained. On the other hand, PEG 1000 produces whitish, very soft, most sticky, and very smooth suppository. Thus, suitable and appropriate combination ratio of PEG 1000 and PEG 6000 is important in the production of an optimum drug delivery with optimum bioavailability of drugs available to the body and also to avoid too hard or too soft suppository.


CONCLUSION

Different composition of base can affect the physical characteristic of suppositories. High amount of PEG 6000 will produce hard and less greasy suppository. However, high amount of PEG 1000 will give soft and greasier suppository. Proper combination of PEG will give the optimum drug released rate.


REFERENCES

Poly(ethylene glycol)”,

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