THE EFFECT OF DIFFERENT AMOUNT OF PEG ON THE PHYSICAL CHARACTERISTICS OF SUPPOSITORY

Introduction:

Suppositories are solid dosage forms of various sizes, appearance (shapes) and weights intended for administration commonly by rectal route, vaginal route or even urethral where they melt, soften or dissolve to exert their effect. Suppositories come in variety of sizes and shapes where they are capable of being easily inserted into the intended orifice without causing undue distention. Moreover, suppositories can be used for two main purposes. The first is to act locally as a protective around the tissue where it is inserted and on the other hand suppository can not only act simply as a vehicle or carrier of an active drug, that we want to be absorbed at site of action but it can also be distributed systematically to produce an effect throughout the entire body.

The suppository usually composed of a medicament incorporated (dissolved or suspended) in a suppository base, this medicament may be intended for retention within the cavity for localized drug effect or to be absorbed for the exertion of systemic effect. For example, rectal localized action such as relief of constipation, pain, itching and inflammation associated with hemorrhoid conditions. Suppositories are indicated for systemic action in pediatric patients and in patients who cannot take or tolerate oral medication due to variety of reasons e.g. to relief nausea, vomiting and pain. The drug must be spread in a suitable base of suppository. Ideal suppository bases should be easily formed by compression or molding; release any medicament readily; melt at body temperature or dissolve or disperse in body fluids; keep its shape when handled; compatible with the drugs, non-irritant and non-toxic.

Polyethylene glycol (PEG) polymers have received much attention as suppository bases 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 mold or compression, in a wide range of hardness and melting point. Moreover, they do not melt at body temperature, but dissolve to provide a prolonged release. Certain PEG 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.

Objectives:

·        To calibrate suppository mould with PEG before preparing medicated suppositories.

·        To determine the effect of different compositions of PEG base on the physical characteristics of suppositories.

3.0 Materials and methodology:

3.1 Apparatus:

           

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

           

3.2 Materials:

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

3.3 Methodology

3.3.1 Calibration of Suppository Molds with PEG Base

For the calibration exercise, 10 g of following proportion PEG 1000 and PEG 6000 had been used.

Ingredients	Percentage	Weight Basis
PEG 1000	60%	6.00 g
PEG 6000	40%	4.00 g

To calibrate the mold with PEG suppository base:

1. A clean and dry mold is taken and the mold is not lubricated.

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

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

4. The cavities are overfilled in the mold and is left to solidify at room temperature.

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

6. The suppositories are weighed and the total weight is recorded. The average suppository weight is calculated.

3.3.2 Preparation of paracetamol suppositories

1. Saturated stock solution of paracetamol is prepared by adding 10 g of paracetamol in 5 mL distilled water.

2. Paracetamol suppository is prepared using the following formulation:

                    

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. Each type of PEG is melted on the steam bath or hot plate, then, the heat is reduced and mixed with other PEG.

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

5.  The cavities are overfilled in the mold and is left to solidify at room temperature.

6. The excess is carefully removed with a hot spatula; the suppositories were removed from the mold.

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

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

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

Results:

Calibration of suppository molds with PEG base.

Mold
Total weight for 6 suppositories	6.457 g
Average weight for 1 suppository	1. 076g

Suppositories	I	II	III
Time taken to melt (min)	47.34	42.11	54.48
Shape	Bullet	Bullet	Bullet
Hardness	Low	Medium	High
Greasiness	High	Medium	Low
Color	Clear White	Clear White	Pale White

Discussion :

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

The calibration of suppository mould is required to be done as each individual mold is capable of holding a specific volume of material in each of its openings. For example, the weight of suppository made up of cocoa butter will differ from the weight of suppository prepared in the same mold with a polyethylene glycol base (PEG) due to the differences in the density of the base materials. Therefore, any addition of medicinal agents alters the density of the base and the weight of the resulting suppository will differ from the suppository that has been prepared with base material alone. This is the reason why a pharmacists calibrates the suppository mold with a common base; to ensure that the medicated suppository will contain proper amount of medicament.

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

The shape for all Paracetamol suppositories are bullet shape because they are made using the same mold. The higher the molecular weight, the more hydroxyl group, the higher its melting point. As a result, the melting point for suppository III, which has 9g of PEG 6000, is the longest and supposedly the melting point point for suppository I is the fastest but somehow our result deviate because suppository II melt faster.  This could be due to error while conducting this experiment.  The same relationship can be used to explain the hardness of the suppositories, the more amount of PEG 6000 the harder the suppository will be.. Suppository I is more greasy than the other suppositories because it contain 9g of PEG 1000. PEG 1000 is more hydrophobic than PEG 6000 so, the higher amount of PEG 1000, the more greasy the suppository will be.

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.

From the graph,it is known that suppositories that have higher amount of PEG 6000 melt less rapidly than others suppositories using lesser amount of PEG 6000.This can be attributed to the physical properties of the suppositories itself, suppositories having high amount of PEG 6000 exhibit increase hardness and brittle properties,which upon contact with water or aqueous solution,disintegrate more easily than those suppositories having lower amount of PEG 6000 and appear soft.

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

            The ingredients used in the suppository formulation is PEG 1000, PEG 6000 and paracetamol. Paracetamol is the active ingredient in the suppository. Paracetamol is also known as acetaminophen. It has analgesic effect and antipyretic effect. It can help to relieve pain and fever. It is typically used for mild to moderate pain.

            Polyethylene glycols are polymers of ethylene oxide and water which has various chain lengths, molecular weights, and physical states. They are chemically stable, nonirritating, and miscible with water and mucous secretions and can be formulated, either by molding or compression, in a wide range of hardness and melting point. The higher the molecular weight of PEG, the harder the suppositories formed and the higher the melting point.. Certain polyethylene glycol polymers may be used singly as suppository bases but, more commonly, two or more PEG with different molecular weights are used to yield a finished product of satisfactory hardness and dissolution time.

Since PEG is a water miscible bases, the suppository will dissolve in body fluids and thus, need not to be formulated to melt at body temperature. Hence, it can be formulated with much higher melting points and thus may be safely stored at room temperature. Formulation with higher amount of PEG 6000 compare to PEG 1000 will take a longer time to melt completely and thus, has slower release rate of drug.

Conclusion:

As a conclusion, different composition in the suppository will affect the physical property and the rate of drug release from the suppository. Higher amount of PEG 6000, the more harder the suppository and the higher its melting point.