Date of Experiment : 5 MARCH 2018
Title : The effect of different amount of PEG on the physical characteristics of suppository.
Introduction :
Threoboma oil or cocoa butter are normally used as suppository base because in large measure it is an ideal base for suppositories. At room temperature, it is a hard, amorphous solid but it can melt into a non-irritating oil at body temperature. Thus it should be kept in a cool and dry place. Polyethylene glycol polymers are water miscible bases. 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.
Objective :
To calibrate suppository mould with PEG before preparing medicated suppositories and to determine the effect of different compositions of PEG based on the physical characteristics of suppositories.
Apparatus and Materials :
3.1. Apparatus
Analytical balance, water bath at 37˚C, hotplate, 4 x 50ml beaker, 1 x 5ml pipette and pipette bulb, 1 x 5ml measuring cylinder, 1 x suppository mould set, 1 x spatula, 4 x weighing boat, 2 x glass rod
3.2. Materials
Polyethylene glycol (PEG) 1000, polyethylene glycol (PEG) 6000, paracetamol, distilled water, liquid paraffin.
Methodology :
Calibration of Suppository Molds with PEG Base
1. 6 g of PEG 1000 and 4 g of PEG 6000 were weighed to be used for this calibration exercise and a clean and dry unlubricated suppository mold were chosen.
2. The 6 g of PEG 1000 were melted on a hot plate before 4 g of PEG 6000 were added.
3. The mixture were removed from the heat and was allowed to cool before being poured into the unlubricated mold.
4. The filled mold were let stand at room temperature until the mixture solidified.
5. The excess were carefully removed with a hot spatula before the suppositories were removed from the mold.
6. The suppositories were weighed and the average suppository weight were calculated.
Preparation of Paracetamol Suppositories
1. Saturated stock solution of paracetamol were prepared by adding 0.1 g of paracetamol in 5 mL distilled water.
2. The suppository mold were lubricated with liquid paraffin.
3. Three types of paracetamol suppository with different composition ratio were prepared following the given formulation.
4. For the type I suppository, 9 g of PEG 1000 were melted on hot plate then added with 1 mL of Paracetamol stock solution. Type II and III suppositories were were prepared using different ratio of PEG 1000 and PEG 6000 as stated in the formulation.
5. The melted mixture were removed from heat and allowed to be cooled down before poured into the lubricated mold.
6. The mold were filled with the mixture and were let in the room temperature until if solidified.
7. The excess mixture were removed using hot spatula before the suppositories were removed from the mold.
8. The shape, texture and color of the suppositories were observed and recorded.
9. Each suppositories were put into separate beaker containing distilled water with constant temperature of 37 °C.
10. The time taken for the suppositories to melt were recorded.
Calibration of Suppository Molds with PEG Base
1. 6 g of PEG 1000 and 4 g of PEG 6000 were weighed to be used for this calibration exercise and a clean and dry unlubricated suppository mold were chosen.
2. The 6 g of PEG 1000 were melted on a hot plate before 4 g of PEG 6000 were added.
3. The mixture were removed from the heat and was allowed to cool before being poured into the unlubricated mold.
4. The filled mold were let stand at room temperature until the mixture solidified.
5. The excess were carefully removed with a hot spatula before the suppositories were removed from the mold.
6. The suppositories were weighed and the average suppository weight were calculated.
Preparation of Paracetamol Suppositories
1. Saturated stock solution of paracetamol were prepared by adding 0.1 g of paracetamol in 5 mL distilled water.
2. The suppository mold were lubricated with liquid paraffin.
3. Three types of paracetamol suppository with different composition ratio were prepared following the given formulation.
4. For the type I suppository, 9 g of PEG 1000 were melted on hot plate then added with 1 mL of Paracetamol stock solution. Type II and III suppositories were were prepared using different ratio of PEG 1000 and PEG 6000 as stated in the formulation.
5. The melted mixture were removed from heat and allowed to be cooled down before poured into the lubricated mold.
6. The mold were filled with the mixture and were let in the room temperature until if solidified.
7. The excess mixture were removed using hot spatula before the suppositories were removed from the mold.
8. The shape, texture and color of the suppositories were observed and recorded.
9. Each suppositories were put into separate beaker containing distilled water with constant temperature of 37 °C.
10. The time taken for the suppositories to melt were recorded.
Results
Part A:
Ingredients
|
Percentage
|
Weight Basis
|
PEG 1000
|
60%
|
6 g
|
PEG 6000
|
40%
|
4 g
|
Mold #
|
5
| |
Total Weight for 6 suppositories
|
6.5422 g
| |
Average weight for one suppository
|
1.0904 g
|
Part 2:
Type
|
PEG 1000 (g)
|
PEG 6000 (g)
|
Shape
|
Texture
|
Color
|
Time taken to start melting (s)
|
I
|
9
|
0
|
Sturdy bullet
|
Smooth,softer, most greasy
|
Most transparent, opaque
|
21.9
|
II
|
6
|
3
|
Sturdy bullet
|
Smooth,soft, greasy
|
Translucent white
|
40.0
|
III
|
0
|
9
|
Sturdy bullet
|
Hard, least greasy
|
Clear white
|
62.0
|
Discussions :
1. Describe the important of calibrating suppository mould before preparing medicated suppository.
- Suppository mould should be calibrated before preparing medicated suppository to ensure that each suppository will contain the correct and proper quantities of active compounds. The volume of each mould will be uniform, but the weight of the produced suppository will be different depending on base used. This is because the difference in the densities of the materials which is suppository base and medicament will produce suppositories with different weights. The base selected can affect the nominal capacity of a mould as well. There are often slight differences between molds and even in the cavities within a mold. Dosage errors that usually occur which are under dose and overdose. Hence, after calibration with the base, we able to determine the correct amount of active compound in the suppositories produced within the mould after calculating the displacement value of the active drug used.
2. Compare the physical appearance of suppositories that are formed and discuss.
| Suppository | PEG 1000 (g) |
PEG 6000 (g)
| Shape | Texture | Color |
I
|
9
|
0
|
Sturdy bullet
|
Smooth,softest, greasiest
|
Opaque
|
II
|
6
|
3
|
Sturdy bullet
|
Smooth,softer, greasier
|
Translucent white
|
III
|
0
|
9
|
Sturdy bullet
|
Hard, least greasy
|
Clear white
|
- From this experiment, different amount of PEG 1000 and PEG 6000 are used in suppositories I, II and III. Hence, it enable us to obtain different physical properties of suppositories. The common physical property that obtain is the bullet shaped of suppositories are obtained as they are poured into the same shaped of suppositories mould. All the suppositories are white in colour as the active ingredient used is Paracetamol which is also white in colour. The only difference that can be observed from these suppositories is the different in transparency. The suppositories I which is the mixture of PEG 1000 and Paracetamol solution are opaque, the suppositories II which containing a mixture of PEG 1000, 6000 and Paracetamol solution are translucent white while the suppositories III contains only PEG 6000 are in clear white color. This is due to increasing amount of PEG 6000 and increasing amount of PEG 1000 used. This is because PEG 1000 is a white paste which is opaque and PEG 6000 is a white flake which is slightly clear by observation. The hardness of suppositories is related to the chemical structure of the overall suppository. Suppositories III which contain only PEG 6000 is the hardest while suppositories I which contain only PEG1000 is the softest among these three suppositories. The hardness of the suppositories increases when the amount of PEG 6000 increases. This is because PEG 6000 contains higher content of hydroxyl groups within the structure so it is more hydrophilic. Since PEG 6000 is a hydrophilic polymer which contains more hydroxyl group so it can form more intra-molecular and inter-molecular hydrogen bonds between PEG molecules, thus increasing the overall structure strength of the suppositories. Other than that, the melting point of PEG 6000 is around 60-63ºC while the melting point of PEG 1000 is around 37-40ºC. Hence, PEG 1000 will melt easier in the human body temperature than PEG 6000. As for the formulation with the lowest amount of PEG 1000 showed the greasiest surface compared to the other suppositories. Therefore, the greasiness of the suppositories are related to the amount and effect of PEG 1000. PEG 1000 is considered more hydrophobic than PEG 6000 so the suppositories I is the greasiest while suppositories III is the least greasy. PEG 1000 has more lipophilic property. Therefore, when the amount of PEG 1000 decreases followed with the increase of PEG 6000, the degree of greasiness decreases. Thus, suppositories with the high content of PEG 1000 will result in the formation of greasier suppositories.
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 6000 amount in the formulation (g) |
0
|
3
|
9
|
| Time required to melt the suppository (min ) |
21.9
|
40.0
|
72.0
|
Different types of PEG will have different molecular weight. The differences in molecular weights will contribute to differences in physical properties such as solubility, freezing point and melting point. PEG melting point is directly proportional to its molecular weight. PEG 1000 with the molecular weight 950-1050 has a lower melting point than PEG 6000 with the range of 5000-7000. Melting point may also increase due to the increasing amount of PEG of the same molecular weight. Theoretically, by 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 will increase the time taken for suppositories to dissolve completely in water bath at 37 degree Celcius.
In this experiment, the time taken for the suppository with zero amount of PEG 6000 to melt is 21.9 seconds. When 3g of PEG 6000 is added to the suppository to melt is recorded at 40.0 seconds and the time needed for suppository with 9g of PEG 6000 to melt is 72.0 seconds. Thus , the results obtained are parallel to the theory. However, there are several precautions should be taken in order to obtain the accurate results. One of the precautions included ensure the suppository are not contaminated during the preparation of the formulation. Next, the formulation should not be heated for too long during the preparation as it may affect the chemical structure of the components in the formulation which eventually affect the time taken for it to melt. Ensure the temperature of the water bath always maintain at 37 degree Celcius when melting the suppositories. Use appropriate apparatus such as 50ml beaker so that the suppositories are submerged entirely in the water bath and the heat is even distributed throughout the suppositories.
4. Function(s) of each ingredients used in the formulation:
-The ingredients used in preparing paracetamol suppository formulation included paracetamol, polyethylene glycol (PEG) 6000, polyethylene glycol (PEG) 1000, distilled water and liquid paraffin.
1. Paracetamol
- Paracetamol is an active ingredient in this formulation that gave the therapeutic effects and are biologically active. It is used for mild to moderate pain relief and as an anti-pyretic.
2. Distilled water
- Solvent to dissolve the paracetamol powder into a stock solution of paracetamol. It also function as a diluent.
3. Liquid paraffin
- Used as a lubricant between the mold and the suppositories. The liquid paraffin forms a film between the wall of the mold and the suppository. This is to ensure the solidified suppository can be easily taken out without sticking to the cavities of the mold in order to prevent the cracking of suppository.
4. Polyethylene glycol (PEG) 1000/ 6000
- PEG polymers are water miscible bases that are non-irritating and miscible with mucous secretions, easy to solidify and has high stability. These properties that make it suitable to be bases for suppositories formulation as the suppository drug can be stored without putting into refrigerator. Other than acting as a carrier base, it also can function as a solubilizer and absorption improver for the drugs or active ingredients in the suppository. When it degrades and the drugs diffusing out from PEG,it eventually increase the effectiveness of dispersion and delivery of drug. If PEG 6000 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 can produce harder suppository. For the low molecular weight PEG, theoretically it would produce a soft suppository that would dissolute and release the loaded drug fast when used alone. Thus, suppository with PEG 6000 as base can solidify faster and harder. It also able to formulate with higher melting point since it is considered a water miscible suppository. Sustained release effect can be achieve if high amount of PEG 6000 is used as it has higher melting point compared to PEG 1000. PEG 1000 and PEG 6000 can be mixed at certain proportions to yield a product with desired hardness, dissolution time and allow optimum drug release rate from the suppository.
Conclusion :
In order to prepare suppository, calibrating suppository mould must be done first to ensure that each suppository will contain the correct and proper quantities of active compounds, thus obtain the same volume. However, weight of each suppository can be different due to difference in density of the composed material. Physical appearance of the suppository in terms of colour, hardness, melting point, and surface of supository are influenced by the type of base used and their ratio in the mixture. Overall, PEG 1000 is a white paste and opaque in appearance which produces more opaque product while PEG 6000 is a white flake and slightly clear in apperance produces more clear product. PEG1000 has fewer amount of hydroxyl group than that of PEG6000 thus has lower interaction between PEG molecules which cause it to be softer than PEG 6000 . Besides, suppository which contains high content of PEG 1000 produces greasier suppository. The difference in the molecular weight between PEG 1000 and PEG 6000 also contributes to difference in melting point. PEG 1000 has lower melting point than PEG 6000 as it has lower molecular weight than PEG 6000. Increasing amount of PEG 6000 will show an increase in melting point.
References :
1 PerkinElmer (2007-2011). Tg and Melting Point of a Series of Polyethylene Glycols Using the Material Pocket.
2 Merck KGaA, Darmstadt Germany and/or its affliates (2018). Poly (ethylene glycol) 1,000. https://www.sigmaaldrich.com/catalog/product/sial/81190?lang=en®ion=MY.
