The effect of different amount of PEG on the physical characteristics of suppository ~ Development of Pharmaceutical Product 2

INTRODUCTION

Suppositories are solid dosage forms with different type of sizes, appearances, and weights to be administered for rectal route delivery. It is used in rectal, vaginal, or urethral drug delivery. It will soften and melt at body temperature and release the drug at the point of insertion. It can act either locally or systemically.

Suppository usually composed of the medicaments incorporated in the base. These medicaments are intended to be retained within the cavity for localized drug effect or to be absorbed and exert systemic effect. Suppositories are indicated for systemic action in pediatric patients and in patients who cannot take or tolerate oral medication due to variety reasons such as to relief nausea, vomiting and pain.

Polyethylene glycol (PEG) is the common suppository base used in recent years because they possess many desirable properties. They are chemically stable, non-irritating, miscible with water and mucous secretions, and can be formulated either by molding or compression, in a wide range of hardness and melting point.

Certain PEG may be used singly as suppository bases but, more commonly the formulas call use compounds of two or more molecular weights mixed in various proportions as needed to yield a finished product of satisfactory hardness and dissolution time.

MATERIALS

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

APPARATUS

Water bath at 37C	Hotplate
4 x 50 mL beaker	1 x 5 mL pipette and pipette bulb
1 x 5 mL measuring cylinder	1 x suppository mould set
1 x spatula	4 x weighing boats
2 x glass rod

METHODOLOGY

A) Calibration of suppository molds with PEG base

To calibrate the mold with PEG suppository base:

Ingredients	Percentage	Weight Basis
PEG 1000	60%	6 g
PEG 6000	40%	4 g

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

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

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

4. The cavities were overfilled in the mold. And left at room temperature until solidified.

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

6. The suppositories weigh was taken, and the total weight was recorded. The average suppository weight was calculated.

Mold #	21
Total weight for 6 suppositories	6.3825 g
Average weight for one suppository	1.0638 g

B) Preparation of paracetamol suppositories

1. Saturated stock solution of paracetamol was prepared by adding 0.1 g of paracetamol in 5 mL distilled water.

2. The following suppository 10 g was prepared 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 the 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 was allowed to cool before pouring into the mold.

5. The cavities in the mold were overfilled. And left at room temperature until solidified.

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

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

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

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

RESULTS

1. Calibration of suppository molds with PEG base

Ingredients	Percentage	Weight Basis
PEG 1000	60%	6 g
PEG 6000	40%	4 g

Table 1: Percentage component and weight basis of suppositories

Mold #	21
Total weight for 6 suppositories	6.3825 g
Average weight for one suppository	1.0638 g

Table 2: Weight of suppositories

2. Preparation of paracetamol suppositories

Suppository	Shape	Colour	Texture
I	Bullet shape	White and certain degree of translucent	Smooth and most sticky
II	Rocket shape	White	Hard and oily
III	Rocket shape	White	Hard

Table 3: Comparison of shape, colour, and texture between the suppositories

Amount of PEG 6000 (g)	0	3	9
Time required to melt the suppository	32 seconds	1 minute and 29 seconds	1 minute and 40 second

Table 4: Time Taken for suppositories to melt.

Graph 1: Time taken required to melt the suppository versus amount of PEG 6000

DISCUSSION

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

Calibration of mold is necessary before preparing suppositories. This is because different bases prepared in the same mold will have different weight as the density of the base is different. Each mold should be calibrated using the base alone, weighing the products and taking the mean weight as true capacity. The calibrating of suppository mold is carried out before preparing medicated suppository is important. This to determine the volume and amount of base used in order to prepare the proper quality of medicaments.

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

Suppository	Shape	Colour	Texture
I	Bullet shape	White and certain degree of translucent	Smooth and most sticky
II	Rocket shape	White	Hard and oily
III	Rocket shape	White	Hard

Suppository I is made up from one type of base which is PEG 1000 and paracetamol as the active compound of the suppository. The amount of PEG 1000 used in this experiment is 9 gram and 1 ml of paracetamol stock. It has certain degree of translucent. The surface of the suppository I is very smooth. It melts easily when in contact with the skin and feels oily when we touch it.

Suppository II is made of combination of two bases which are PEG 1000 and PEG 6000 and paracetamol as its active pharmaceutical formulation. The amount of PEG 1000 used in this experiment is 6 grams while PEG 6000 is 3 grams and 1 ml of paracetamol stock. The suppository II is harder than suppository I but still softer than suppository III. The suppository does not melt easily when in contact with the skin if we compared it with the suppository I. Both suppository II and III are opaque and white in colour.

Suppository III is made from one type of base, PEG 6000 and paracetamol. The amount of PEG 6000 used in this experiment is 9 grams and 1 ml of paracetamol stock. Suppository III is the hardest and does not melt when in contact with the skin. This is because PEG 6000 contains higher content of hydroxyl groups within the structure and its bind strongly with its own structure molecule.

The greasiness of suppository depends on the base use. For example, when the amount of PEG 1000 decreased, the degree of greasiness also decreases. PEG 1000 is less hydrophilic and more lipophilic.

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.

Amount of PEG 6000 (g)	0	3	9
Time required to melt the suppository (min)	0.32	1.29	1.40

This experiment was carried out by varying the ratio of bases in paracetamol suppositories compounding namely polyethylene (PEG) 1000 and PEG 6000 in order to investigate the time needed for the suppositories to melt in water bath with constant temperature.

PEG has a wide range of molecular weight which also influences its melting point. Its melting point is directly proportional to its molecular weight. PEG 1000 has a lower melting point than PEG 6000. 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.

Theoretically, increasing the amount of PEG 6000 from 0 g to 9 g in the formulation of suppositories will show an increase of melting point which prolongs the time taken for suppositories to melt in water bath. The result from the experiment showed an increase in the length of time (1.29 min) for PEG 6000 3g suppository to melt compared to PEG 6000 0g suppository (0.32 min). The result also showed an increase in the length of time (1.40 min) for PEG 6000 9g suppository to melt compared to PEG 6000 3g. The results obtained were parallel with the theory.

The melting point of PEG increases when the molecular weight of PEG and the amount of PEG increase. Higher amount of heat energy is needed to overcome the stronger intermolecular force of attraction between the molecules in suppository as the molecular weight and amount of PEG increase. Thus, time taken for the suppository to melt also increases. On the other hand, the increase in the amount of PEG 6000 in the formulation increases the insolubility in the water and hence the time required to dissolve in water becomes longer. This is because PEG 6000 has lower tendency to dissolve in water than PEG 1000. Hence, the suppository containing higher amount of PEG 6000 takes longer time to melt under the constant temperature of 37%.

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

The ingredients used in preparing paracetamol suppository formulation included paracetamol, polyethylene glycol (PEG) 6000, polyethylene glycol (PEG) 1000, distilled water and liquid paraffin.

Paracetamol is the active ingredient whereby it will give therapeutic effect to the patient. Next, PEG 6000 is used as a suppository base. PEG is easy to solidify and has high stability, thus it is suitable as a suppository base because suppository drug can be stored without putting into refrigerator. If compared with PEG 1000, PEG 6000 is more favorable as PEG 6000 has higher molecular weight than PEG 1000. The higher the molecular weight of PEG, the harder the suppository that can be made. Hence, the suppository can solidify faster and become harder if PEG 6000 is used. It can be formulated with higher melting point since it is considered a water miscible suppository. This also indicates that high amount of PEG 6000 can have sustained release effect if compared with low amount of PEG 6000. Directly, it does give effect on the rate of absorption of suppository.

Distilled water is used in this experiment to dissolve paracetamol in preparing saturated stock solution of paracetamol as paracetamol is a water-soluble substance. Meanwhile, liquid paraffin is essential to lubricate the suppository mold. By lubricating the suppository mould, the solidified suppository can be easily taken out from the mould. Without the help of lubricating oil, the suppository will stick to the wall of mould tightly which will lead to cracking of suppository during attempts to remove it from the mould.

CONCLUSION

Different composition of base can affect the physical characteristic of suppositories. It can be observed through their physical appearance, hardness, greasiness and ease of melting. The suppository with the highest amount of PEG6000 has clear white in color, very hard, lack of greasy but are insoluble in water as time taken for the melting of suppositories is longer.

REFERENCE

Saturday, March 17, 2018