EXPERIMENT 1 : THE EFFECT OF DIFFERENT AMOUNT OF PEG ON THE PHYSICAL CHARACTERISTICS OF SUPPOSITORY

Title: The effect of different amount of PEG on the physical characteristics of suppository

Date: 7 March 2017

Objectives:

1) To calibrate suppository mould with PEG before preparing medicated suppositories.

2) To determine the effect of different composition of PEG base on the physical characteristics of suppositories.

Introduction:

Suppositories are solid dosage forms of various sizes, appearance (shapes) and weights intended for administration by rectal route where they melt, soften or dissolve to exert their effect. They are capable of being easily inserted into the intended orifice without causing undue distention.

            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 haemorrhoid conditions. Suppositories are indicated for systemic action in paediatric 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 moulding; release any medicament  readily; melt at body temperature or dissolve or disperse in body fluids; keep its shape when handled; compatible with 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 secretion, and can be formulated, either by moulding 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.

Apparatus:

Analytical balance                                                                  1 x Suppository mould set

Water bath at 37 ͦ c                                                                  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

Materials:

Polyethylene glycol (PEG) 1000                                            Distilled water

Polyethylene glycol (PEG) 6000                                            Liquid paraffin

Paracetamol

Procedures:

1. Calibration of suppository moulds with PEG base

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

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

Steps to calibrate the mould with PEG suppository base:

1. A clean and dry mould is taken. Do not lubricate the mould.
2. PEG 1000 is melted on a steam bath or hot plate, then, the heat is reduced and mixed in the other PEG.
3. The mixture is removed from the heat and it is allowed to cool before pouring into the mould.
4. The cavities in the mould is overfilled and let stand at room temperature until solid.
5. The excess is removed carefully with a hot spatula; then the suppositories are removed from the mould.
6. The suppositories is weighed and the total weight is recorded. The average suppository weight is calculated.

Mold
Total weight for 6 suppositories=	5.8366g
Average weight for one suppository=	0.9728g

2. Preparation of paracetamol suppositories

1. Saturated stock solution of paracetamol is prepared by adding 10g of paracetamol in 5 ml distilled water.
2. The following paracetamol suppository (10g) is prepared by 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 is melted on a steam bath or hot plate, then, the heat is reduced and mixed in the other PEG.
4. The mixture is removed from the heat and it is allowed to cool before pouring into the mould.
5. The cavities in the mould is overfilled and let stand at room temperature until solid.
6. The excess is removed carefully with a hot spatula; then the suppositories are removed from the mould.
7.  The shape, texture and colour of the suppositories is observed.
8. Each of the suppositories is putted into a separate beaker containing distilled water (10 ml and pre-warmed at 37 ͦ c) and then, the beaker is putted into a water bath (37 ͦ c).
9. The time for the suppositories to melt is recorded.

Results:

3.3.1 Calibration of Suppository Molds with PEG Base

Mold number	6
Total weight for 6 suppositories	5.8366 g
Average weight for one suppository	0.9728 g

3.3.2 Preparation of paracetamol suppositories

Suppository	I	II	III
Shape	Bullet-like shape	Bullet-like shape	Bullet-like shape
Colour	Dull white	Shiny white	White
Texture	Soft, greasy, sticky	Hard, smooth, slightly greasy	Hard, rough, less greasy

Table 1: Physical appearance of suppository

Suppository	PEG 1000 (g)	PEG 6000 (g)	Paracetamol stock solution (mL)	Total (g)	Time taken for suppository to start melt (min)
I	9	0	1	10	3:45
II	6	3	1	10	4:42
III	0	9	1	10	8:20

Table 2: Time taken for suppository to start melt

Suppository 1

Suppository 2

Suppository 3

Questions:

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

Calibration of mould is necessary before preparing suppositories and pessaries since the capacity of mould varies with different capacities. A suppository mould is filled by volume, but the suppository is formulated by weight. The volume of a suppository from a particular mould is uniform but its weight can vary when a drug is present due to difference in densities between the drug and base. Therefore, adding of a medicament results in the altering of weight of the suppository. This is why the density of the material is used to calculate the volume of base required. Thereby, calibrating suppository mould for the usual base is necessary to prepare medicated suppositories each having the proper quantity of medicaments. To calculate the volume of moulds, each mould should be calibrated using the base alone, weighing the suppository products and taking the mean weight as true capacity. Their volumes are determined by melting and the density is then computed for particular base. In extemporaneous preparations, the amount of base required is determined by subtracting the volume of medicaments from the total volume of mold. This procedure is repeated for each base.

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

Certain Polyethylene Glycol Polymers (PEG) are used singly as suppository bases but, more commonly, these polyethylene glycols can be blended together to produce suppository bases with varying melting points, dissolution rates and physical characteristics. PEG base is hydrophilic in nature, slowly dissolves in the aqueous secretions and provides a slow continuous release of medicament. Because of its high melting point which is generally above 42⁰C, they do not melt in the body cavity, rather they gradually dissolve and disperse, releasing the drug slowly to provide a more prolonged release. PEG do not require cool storage and they are satisfactory for use in hot climate. They even solidify quickly after melting. Even with the moulds did not get lubricated, the base did not stick to the wall of the mould since they contracted significantly on cooling. They are easily moulded and removed from the mould with easy handling. Ideally, it should shrink so that it comes out easily from the mould without the use of any lubricants. Moreover, the shape of suppositories still remain intact while handling and should maintain their shape throughout their shelf-life when stored at the temperature indicated on the label.

The PEG used in the experiment is PEG 1000 and PEG 6000. The suppository products formed show physical appearances of having the same bullet-like shaped because of the same shape and size of the mould been used in the experiment. As for the colour, suppository III shows a much whiter color as compared to the other suppositories because of the absence amount of PEG 1000. Thus, it can be concluded that PEG 6000 is the one that shows the significant whitish color. Moving on to the texture of the products, suppositories III have shown a significant harder, rough and less greasy texture in comparison to the other two products. This is due to the amount of base incorporated into the formulation. PEG 6000 is more hydrophilic in nature so the higher the amount of PEG 6000 in the formulation, the less greasy the products are. Besides, PEG 6000 also has a property of higher melting point than PEG 1000, thus contributing to the hardness of the suppositories formed. Therefore, higher proportions of high molecular weight polymers produce preparations which release drug slowly and are also brittle.

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

PEG 6000 amount (g)	0	3	9
Time (min)	3.45	4.42	8.20

In the experiment, the formulation of suppository Paracetamol containing two type of bases which are polyethylene (PEG) 1000 and polyethylene (PEG) 6000.

Polyethylene glycols (PEG) are available in average molecular weight ranging from 200 to 8000. The higher the molecular weight of PEG will form a harder suppositories compared to lower molecular weight PEG. Hence, PEG 6000 will create a more solid suppository and required a lot of time to melt rather than PEG 1000.

Based on the graph, as the amount of PEG 6000 in the formulation increases, the time taken for the suppository also increases. From 0g to 3g amount of PEG 6000, the time taken increase fairly, but from 3g to 9g amount of PEG 6000, there is a sharp increase. The melting point of suppository is proportional to their molecular weights.

This is due to the different amounts of 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 high amount of 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. Accordingly, melting point increases as molecular weight increases. In addition, increase amount of PEG used will increase the time taken for formulation to melt.

4. Describe functions of each ingredients used in the suppository formulation.

The ingredients that are used in the experiment for the suppositories are Paracetemol, PEG 1000 and PEG 6000. The Paracetamol 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.

Both PEG 1000 and PEG 6000 are polyethylene glycols (PEG) polymers. Both function as suppository base for the formulation in the experiment. Polyethylene Glycol (PEG) polymers are water miscible type of bases. Various active ingredients can be dissolved in PEGs and have a good bioavailability. They act as carrier bases, solubilisers and absorption improvers for the drugs. PEG 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.

Commonly, formulation used of compounds of two or more molecular weights mixed in various proportions as needed to yield a finished product of satisfactory hardness and dissolution time. 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.

Conclusion:

In conclusion, different amount of combination of PEG 1000 and PEG 6000 affects the physical characteristics of the suppository such as texture and colour. Besides, the time taken for the suppositories to melt are also affected as well. The higher the amount of PEG 6000, the suppository will be harder and need more time to melt and release the drug. Less amount of PEG base in the suppository make them more transparent compare to the other that have more PEG base.

References:

1. N. Dand. (Aug 25, 2015). Pharmaceutical dosage form - suppositories. Retrieved March 15, from https://www.slideshare.net/nehadand/suppositories-52034307 

2. R. K. Sharma. (Feb 8, 2013). Pharmaceutical suppositories. Retrieved March 15, from https://www.slideshare.net/rks19761/pharmaceutical-suppositories 

3. R.P. Shrewsbury. (1996-2007). Retrieved March 15, from http://pharmlabs.unc.edu/labs/suppository/labs.htm