The effect of different amount of PEG on the physical characteristics of suppository.

UNIVERSITI KEBANGSAAN MALAYSIA

DEVELOPMENT OF PHARMACEUTICAL PRODUCTS II

(NFNF 2283)

PRACTICAL 1

GROUP: B5

GROUP MEMBER:

1. MUHAMMAD AIMAN AZIZI BIN SHAIFUL ANUAR (A163457)
2. NUR NADHIRAH BINTI MUHAMMAD SUKRI (A163377)
3. KANMMANI A/P SELVAM (A162878)
4. VENNILA A/P MUNIANDY (A163013)

TITLE

The effect of different amount of PEG on the physical characteristics of suppository.

INTRODUCTION

Suppositories are medicated, solid bodies of various sizes and shapes suitable for introduction into body cavities. The medicament is incorporated into a base such as cocoa butter which melts at body temperature, or into one such as glycerinated gelatin or PEG which slowly dissolves in the mucous secretions. Suppositories are suited particularly for producing local action, but may also be used to produce a systemic effect or to exert a mechanical effect to facilitate emptying the lower bowel. The advantage of suppository is that it can prevent first pass effect, and to avoid the digestive enzyme and thus increase bioavailability.

A good base should not be toxic, does not produce irritation, does not react with the drug, and easy to form into a suppository. It should also dissolve or disintegrate in the presence of mucous secretions or melt at body temperature, 37⁰C to allow for the release of the medication. Different base composition will affect the rate and release limit of a drug from suppository.

Polyethylene glycol polymers are water miscible bases. In cases where systemic action is expected, it is preferable to incorporate the ionized form instead of the nonionized form of the drug, in order to maximize bioavailability. Polyethylene glycol polymers are used as suppository base because of its desirable properties such as they are chemically stable, non-irritating, miscible with water and mucus secretion and can be formulated easily either by molding or compression. They do not melt at temperature but dissolve to provide a more prolonged release than cocoa butter.

In this experiment, we are instructed to do several suppositories formulation with different composition of suppositories’ base. The result will be discussed.

APPARATUS AND MATERIALS

Analytical balance	1 x Suppository mould set
Water bath at 37oC	1 x Spatula
Hotplate	4 x Weighing boats
4 x 50 mL beaker	2 x Glass rod
1 x 5 mL pipette and pipette bulb
1 x 5 mL measuring cylinder

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

PROCEDURE

Calibration of Suppository Molds with PEG Base

For this calibration exercise, 10 g of the following proportions of PEG 1000 and PEG 6000 was used.

Ingredients	Percentage	Weight Basis
PEG 1000	60%	__________ g
PEG 6000	40%	__________ g

To calibrate the mold with PEG suppository base:

1. A clean and dry mould was taken. The mould was not lubricated.

2. PEG 1000 was melted on a steam bath or hot plate, then, the heat was reduced and mixed in the other PEG.

3. The mixture was removed from the heat and allowed to cool before pouring into the mold.

4. The cavities in the mold were overfilled. It was allowed to stand at room temperature until solid.

5. The excess was removed carefully with a hot spatula; then the suppositories were removed from the mold.

6. The suppositories were weighed and the total weight was recorded. The average suppository weight was calculated.

Mold #	__________
Total weight for ____ suppositories =	_________ g
Average weight for one suppository =	_________ g

3.3.2 Preparation of paracetamol suppositories

1. A saturated stock solution of paracetamol was prepared by adding 10 g of paracetamol in 5 mL distilled water.

2. The following paracetamol suppository was prepared (10 g) using the formulation below:

Suppository	PEG 1000 (g)	PEG 6000 (g)	Paracetamol stock solution (mL)	Total (g)
I	9	0	1	10
II	6	3	1	10
III	0	9	1	10

3. One type of PEG was melted on a steam bath or hot plate, then, the heat was reduced and mixed in the other PEG.

4. The mixture was removed from the heat and allowed to cool before pouring into the mold.

5. The cavities in the mold were overfilled. It was allowed stand at room temperature until solid.

6. The excess was removed with a hot spatula; then the suppositories were removed from the mold.

7. The shape, texture and color of the suppositories were observed.

8. Each of the suppositories was put into a separate beaker containing distilled water (10 mL and pre-warmed at 37^oC) and then, the beaker was put into a water bath (37^oC).

9. The time for the suppositories to melt was recorded.

RESULTS

Table A: The Average Weight of Calibration Suppositories

Mold
Total weight for 6 suppositories	6.1127 g
Average weight for one suppository	1.0188 g

Table B: Physical Appearance of the Suppositories with Different Formulation

Suppositories	Calibration	I	II	III
Shape	Well-filled bullet shaped	Well-filled bullet shaped	Well-filled bullet shaped	Well-filled bullet shaped
Texture	Smooth and hard	Smooth and soft	Smooth and hard	Rough and hard
Colour	Shiny white	Cloudy with a little transparent	Shiny white	Whitish
Greasiness	Greasy	Very greasy	Greasy	Less greasy

Suppository I

Suppository II

Suppository III

Table C: Time Taken for the Suppositories to Melt Completely

Suppository	I	II	III
PEG 6000 amount	0	3	9
Time (minute)	31.5	70	46.26

DISCUSSION

1. Describe the important of calibrating suppository mould before preparing medicated suppository

The importance of calibrating suppository mould before preparing medicated suppository is to ensure that the suppository formed is in good shape and to prevent the breaking of suppository when removed from the mould. The mould should be lubricated well to ease the removal of the suppository from the mould.

2. Compare the physical appearance of suppositories that are formed and discuss

From the results obtained, suppository I has a smooth and soft texture compared to suppository II which is smooth and hard and suppository III which is rough and hard. This might be caused by the high percentage of PEG 1000 in suppository I which has a lower molecular weight compared to PEG 6000. Besides that, suppository I has a cloudy with little transparent colour whereas suppository II is shiny white and suppository III is whitish. This can be concluded that higher percentage of PEG 6000 will produce whiter colour due to its molecular weight. Next, suppository I has the highest greasiness compared to suppository II which is greasy and suppository III which is the least greasiness. This proves that lower molecular weight produces higher greasiness.

3. Plot a graph of time required to melt the suppository vs the amount of PEG 6000 in the formulation. Compare and explain the results.

Polyethylene glycol (PEG) is commonly used as base for suppository formulation due to its non-irritate and chemically stable characteristics. This experiment is conducted by varying the amount of PEG 6000 in the formulation in order to identify the time required for each of the suppositories to melt in water bath at 37°C. PEG has a wide range of molecular weight which also influences its melting point. The melting point is directly proportional to molecular weight. PEG 1000 has a lower melting point than PEG 6000 with the range of molecular weight 950-1050 and 5000-7000 respectively. Melting point may also increase due to the increasing amount of PEG of the same molecular weight. Thus, the differences in molecular weight and ratio of PEGs used in formulation of suppository are going to affect the physical and chemical stability of suppositories produced.

From graph above, we can say that the suppository with 0 g of PEG 6000 have fastest time taken to melt if compared with suppositories with 3 g and 9 g of PEG 6000 respectively. This is because of the absence of PEG 6000 which causes the melting point of this suppository is lowest than the others. In addition, this suppository also have smooth and soft texture which make it easily melt. Theoretically, increasing the amount of PEG 6000 from 0 g to 9 g in the formulation of suppositories supposedly show an increase of melting point which prolongs the time taken for suppositories to dissolve completely in water bath. In this experiment, based on the graph, the time taken for suppositories to melt was increased from suppository which contain 3 g of PEG 6000 but the time taken was decreased with suppository which contain 9 g of PEG 6000. The results obtained were not parallel with the theory. These may be due to errors that might be occurred during the experiment. One of the errors is that the formulations were heated for too long during compounding. This may affect the chemical structure of components in the formulations which then affect the melting point and length of time taken for the suppositories to dissolve. Besides, the temperature of water bath might not stay at its constant temperature which is 37°C. The temperature of water bath needs to be constant as the suppositories need to be dissolved in a water bath of constant temperature to ensure accurate results.

4. Describe function(s) of each of ingredients used in the suppository formulation.

The ingredients that are used in the suppository formulation are paracetamol, polyethylene glycol (PEG) 6000, polyethylene glycol (PEG) 1000 and liquid paraffin. Paracetamol act as active ingredient in the suppository formulation which function as antipyretic and analgesic medication. Paracetamol is widely used to reduce fever. Next ingredient is polyethylene glycol (PEG) 6000 and polyethylene glycol (PEG) 1000. PEG act as suppository base because they are chemically stable, non-irritating, miscible with water and mucous secretions and can be formulated either by moulding or compression in a wide range of hardness and melting point. Lastly, liquid paraffin is used as lubricant to lubricate the suppository mould. By doing this, the solidified suppository can be easily taken out from the mould. Without lubricant, the solidified suppository might stick to the wall of the suppository mould.

CONCLUSION

Different amount of PEG base in suppository formulations affects the physical characteristics of the suppository product. Lower molecular weight PEG base will give lower melting point of the suppository compared to the higher molecular weight PEG base.

REFERENCES

1. Sharif, M. R., Haji Rezaei, M., Aalinezhad, M., Sarami, G., & Rangraz, M. (2016, January 13). Rectal Diclofenac Versus Rectal Paracetamol: Comparison of Antipyretic Effectiveness in Children. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753024/

2. (n.d.). Retrieved from https://pharmlabs.unc.edu/labs/suppository/bases.html