NFNF2283 : Suppositories

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

1. Introduction:

Suppository is a solid but readily meltable cone or cylinder of usually medicated material for insertion into a bodily passage or cavity (as the rectum, vagina, or urethra).It is usually medicated, which is solid at room temperaturesbut melts at body temperature. Suppository bases usually used are theobroma oil, glycerinated gelatin, hydrogenatedvegetable oils, mixtures of polyethylene glycols of various molecular weights, and fatty acid esters of polyethyleneglycol.Suppositories are manufactured in a variety of shapes. For example, rectal suppositories for adults are tapered at one end and usually weigh about 2 grams. Infant rectal suppositories usually weight about 1 gram or about half that of adult suppositories.

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 is a condensation polymers of ethylene oxide and water with the general formulaH(OCH₂CH₂)_nOH, where n is the average number of repeating oxyethylene groups typically from 4 to about 180. The low molecular weight members from n=2 to n=4 are diethylene glycol, triethylene glycol and tetraethylene glycol respectively, which are produced as pure compounds. The low molecular weight compounds upto 700 are colorless, odorless viscous liquids with a freezing point from -10 C (diethylene gycol), while polymerized compounds with higher molecular weight than 1,000 are waxlike solids with melting point upto 67 C for n 180.

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 molding 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.

2. Objectives:

1. To calibrate suppository mould with PEG before preparing medicated suppositories.
2. To determine the effect of different compositions of PEG base on the physical characteristics of suppositories.

3. Materials and methodology:

3.1 Apparatus:

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

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 this calibration exercise, use 10 g of the following proportions of PEG 1000 and PEG 6000.

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

To calibrate the mold with PEG suppository base:

1. A clean and dry mold is taken. Lubrication did not done in the mold. 
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 allowed to cool before pouring into the mold. 
4. The cavities are overfilled in the mold. Let stand at room temperature until solid.
5.  The excess is removed carefully with a hot spatula; then the suppositories were removed from the mold. 
6. The suppositories were weighed and the total weight iss recorded. The average suppository weight is calculated.

Mold #	__________
Total weight for  5  suppositories =	5.2598     g
Average weight for one suppository =	1.0520     g

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. The following paracetamol suppository (10 g)is 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 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 allowed it to cool before pouring into the mold.

5. The cavities in the mold are overfilled. Let stand at room temperature until solid. 

6. Excess is carefully removed with a hot spatula; then the suppositories from the mold are removed. 

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

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

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

Discussion:

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

Calibrating of the suppository mould is to ensure the suitable or optimum quantity of PEG can be obtained and to be used in preparing the medicated suppository formulation. 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.

The desired solidity can be controlled 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.

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

Formulation:

Suppositories	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

The result

Suppositories	Shape	Hardness /Softness	Stickiness	Smoothness	Colour
I	Bullet-shape	Soft	Most sticky	Smooth	Even-white
II	Bullet-shape	Hard	Sticky	Smooth	White
III	Bullet-shape	Hardest	Less sticky	Smooth	Uneven white

Based on the result obtained, it is shown that the ratio between PEG 1000 and PEG 6000 will determine the physical appearance of suppositories that will be formed. Both act as excipient (pharmacologically inactive substance) in the suppositories formulation. This is because it has low toxicity with systemic absorption less than 0.5% and allow for better solubility for certain drugs.

In this experiment, it is observed that as the composition of PEG 1000 in the suppositories formulation increases, the softness of suppositories will increase. PEG 1000 is soluble in water and organic solvents. Its melting point is between 35°C to 40°C and has a density of 1.101 g/dm³. The suppository will melt at normal human body temperature which is around 37°C once it is been inserted into the rectum. The stickiness and smoothness shows some increase. This can be seen in suppository I where the suppository is soft, most sticky and most smooth.

On the other hand, as the composition of PEG 6000 in the suppositories formulation increases, the hardness of suppositories will increase. PEG 6000 is soluble in water and aromatic hydrocarbons. It has a melting point between 60°C to 63°C where at normal human body temperature, the suppository will hardly melt in the rectum after the insertion. The stickiness and smoothness shows some decrease. This can be seen in the suppository III where the suppository is the hardest, less sticky and less smooth.

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.

PEG amount (g)	0	3	9
Time (min)	83.6	55.2	64.8

                      

The graph above showed the time taken to melt the suppositories against the amount of PEG 6000 used in the suppository. Polyethylene glycol or PEG is a synthetic polymer and available in a range of molecular weight and a water soluble base which is highly water miscible . PEG 6000 which is higher in molecular weight than PEG 1000 will exist in waxy solid form while PEG 1000 will exist as greasy semisolid. Thus , with these two combination will lead to differences in the drug release rate and the physiochemical properties which in this experiment will lead to different rate of the suppository to melt. The time taken for the suppository to melt influenced by the PEG 6000 which function as the lipophilic base. Hence, as the amount of PEG 6000 used in the suppository increases, it will become more insoluble in water , thus required more time to dissolve in water. Based on the experiment , the graph indicated that the time for the suppository to melt decrease gradually as the amount of PEG 6000 increases in the suppository until 3 g of PEG 6000 been used. And the graph indicated that there is an increases in the time taken for the suppository to melt when 9 g of PEG 6000 is used. Based on the theory ,the time taken for the suppository to melt will increase as the amount of the PEG 6000 increases. Thus , the result obtained has some error. This may due to some experimental error. Such as , the water bath temperature is not accurately fixed at 37 degree celcius which may caused the time taken for the suppository to melt is not accurate. The suppository may be has been dissolved or contaminated with water before it is inserted into the water bath that causes it to start to melt earlier than it supposed to be.

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

Substances used in suppository formulation this experiment such as PEG 1000, PEG 6000 and Paracetamol.

PEG 1000 and PEG 6000 are water-miscible suppositories bases. Numerous active ingredients can be dissolved in PEGs and have a good bioavailability. They act as carrier bases, solvent and absorption improvers for the drugs. Different ratios of low and high molecular weight of PEG can be altered to control the hardness of the suppositories. PEG 6000 will form harder suppositories compared to lower molecular weight PEG, PEG 1000.PEG has low toxicity with systemic absorption less than 0.5%.

Paracetamol in the suppository formulation acts as active ingredient. It is the main substance in the drug formulation which play the major role in contributing to the required drug therapeutic effects in the body.

  

Conclusion

To conclude, in order to produce an ideal suppository, we need to recount the amount of PEG 1000 and PEG 6000 needed in the suppository formulation. An ideal suppository should be neither too hard, nor too soft, neither too sticky, nor too unsticky, and neither too smooth, nor too rough. Everything must be intermediate in between two stages.

References:

1.http://chemicalland21.com/industrialchem/organic/POLYETHYLENE%20GLYCOL.htm

2.http://www.merriam-webster.com/medical/suppository

3.  Su, A. P.; Zhou, Y.; Yao, Y. H.; Yang, C. M.; Du, H. A facile rout to synthesis lamellate structure mesoporous alumina using polyethylene glycol 6000 (PEG, molecular weight= 6000) as structure directing agent. Microsporous Mesoporous Mater. 2012, 159, 36-41.

4.  Drugs.com. polyethylene Glycol 6000  http://www.drugs.com/inactive/polyethylene-glycol-6000-274.html.