The Effect of Different Amount on PEG on the Physical Characteristics of Suppository


NFNF2283: Development of Pharmaceutical Product 2

Experiment 1

The Effect of Different Amount on PEG on the Physical Characteristics of Suppository

HAW TONG LIANG | KHAW SIN MEI | SITI HAJAR MARYAM DHUOHA BINTI MOHD NOOR | LOI TEK MING | MAISARA BINTI MOHAMAD ZUHRI

1.    Introduction

A suppository is a solid dosage form that is inserted into the rectum which is called rectal suppository. Besides, suppositories also can used in vagina as vaginal suppository or urethra as urethral suppository. It dissolves or melts in the body and exerts local or systemic effects. Suppositories are used to deliver both systemically and locally acting medications. It has various sizes, appearance (shapes) and weights that can be easily inserted into the intended orifice without causing undue distension.

Suppository is usually used to relieve occasional constipation in adult. It also provides localized action to relief of 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, for example 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 the drugs, non-irritant and non-toxic.

Suppository bases are classified according to their composition and physical properties. Generally, there are two types of suppository bases, oleaginous (fatty) bases and water soluble or miscible bases. The examples of oleaginous bases include theobroma oil or cocoa butter and synthetic triglyceride mixtures while the example of water miscible bases are those containing glycerinated gelatin or the polyethylene glycol (PEG) polymers.

Recently, polyethylene glycol polymers are most common used because they are chemically stable, non-irritating, miscible with water and mucous secretions, and can be formulated, either by moulding or compression, in a wide range of hardness and melting point. It provides a prolonged release properties compare to other suppository base such as cocoa butter. To yield a finished product of satisfactory hardness and dissolution time, it can be mixed in various proportions with two or more molecular weights. Since PEG is water miscible, it can be formulated with much higher melting point because it can dissolve in the body fluid even the melting point does not reached. 

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                                2 x suppository mould set

Hotplate                                                  2 x spatula

Water bath at 37°C                               4 x weighing boats

4 x 50ml beaker                                     2 x glass rod

1 x 5ml pipette and pipette bulb          2 x evaporating dish

1 x 5ml measuring cylinder



3.2 Materials

Polyethylene glycol (PEG) 1000         Distilled water

Polyethylene glycol (PEG) 6000         Paracetamol

Liquid paraffin   



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
6.1370g
PEG 6000
40
4.0159g

          To calibrate the mold with PEG suppository base:

1.    A clean and dry mold was taken. Do not lubricate the mold.

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

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

4.    The cavities were overfilled in the mold and let stand at room temperature until solid.

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

6.    The suppositories were weighed and the total weight was recorded. The average suppository weight was calculated.







Mold #
1.0
Total weight for 6 suppositories
6.6794g
Average weight for 1 suppository
1.1132g



3.3.2     Preparation of paracetamol suppositories

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

2.    The following paracetamol 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 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 were overfilled in the mold. Let stand at room temperature until solid.

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

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

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

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



3.4 Results

3.4.1     Calibration of suppository molds with PEG base

Mold #
1.0
Total weight for 6 suppositories
6.6794 g
Average weight
1.1132 g



3.4.2     Preparation of paracetamol suppository

Suppository
I
II
III
Shape
Bullet-shaped
Bullet-shaped
Bullet-shaped
Texture
Squishy and brittle
Hard
Harder and not brittle
Colour
White
White
White
Time taken to melt (s)
0.56
5.23
6.15





4.    Discussion:

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

Individual mould is capable of holding certain volume of substance because of the difference in the densities of suppository base and medicament. Thus, it is necessary to calibrate the suppository mould before preparing medicated suppository in order to ensure accurate dosing.



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



Suppository
Shape
Colour
Texture
I
Bullet
White
Solid, Squishy, brittle
II
Bullet
White
Solid, Hard
III
Bullet
White
Solid, Harder, not brittle



All suppositories are solid, bullet-shaped and in white colour. But, suppository I is squishy and brittle compared to suppository II and suppository III because it contains Polyethylene glycol (PEG) 1000 only which is a lower molecular weight. The hardness of suppository is increasing with an increase in the molecular weight of the base. Hence, suppository III is the hardest and not easily brittle because it contains polyethylene glycol (PEG) 6000. Plus, suppository III took the longest time to start melting in the temperature of 37 degree celcius.

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 has a greater average molecular weight than that of PEG 1000. Besides, PEG 6000 has the lower tendency to absorb water compared to PEG 1000. The amount of PEG 6000 is inversely proportional to the ability of suppository to dissolve in water. Thus, the higher the content of PEG 6000, the more difficult the formulation of suppository to dissolve in the distilled water. Theoretically, the molecular weight of PEG (Polyethylene glycols) is directly proportional to the melting point of the suppository. From this statement, we can conclude that PEG 6000 has more influence than that of PEG 1000 on the melting point of suppository since PEG 6000 has a higher molecular weight than that of PEG 1000.
Based the graph above, we can conclude that the amount of PEG 6000 is affecting the melting point of the suppository and the graph is nearly fit the theoretical pattern. The greater the molecular weight of PEG 6000, the higher the melting point of the suppository, the longer the time needed to melt the suppository in distilled water at water bath (37°C). There is an attraction force between paracetamol and PEG particles, this force is enhanced when the concentration of PEG 6000 is increased, and this results in increasing time to break the bonds between the particles of the compound. Besides, the increase in the content of PEG 6000 in the suppository can lower its water solubility and this will require more time to dissolve in water.
The suppository containing 0g of PEG 6000 (Suppository I) shows lowest time needed to melt it (0.56s), this value is differed too much from the suppository than contained 3g of PEG 6000 (Suppository II) and 9g of PEG 6000 (Suppository III). There are several errors that distributed to this case. For instance, one of the member did not wear glove when he was handling the suppository, as the temperature of human palm is around 36.5–37.5 °C, therefore it can cause the suppository to melt a little before placing it to the pre-warmed distilled water. (37°C). As a result, the time taken required to melt the suppository is further minimized when compared to other suppositories. Students should wear glove throughout the experiment to avoid inaccuracy of experiment’s results. Next, we should do more suppository for each set and get average value from it to improve accuracy of results.
PEG amount (g)
0
3
9
Time (min)
0.56
5.23
6.15

4.    Describe function(s) of each ingredients used in the suppository formulation.
The ingredients used in the suppository formulation are paracetamol and polyethylene glycol (PEG). Paracetamol is the active ingredient that will exert the therapeutic effects in the body. Paracetamol Suppositories are used to treat pain and high temperature (fever) in children from the age of 6 years. They are used by children who find it difficult to take paracetamol as tablets or syrup. In this experiment, we used two types of PEG: PEG 6000 and PEG 1000. They are differ in molecular weight where PEG 6000 has higher molecular weight than that of PEG 1000. They are both inactive ingredients in the suppository formulation. They are used as suppository bases (water miscible bases) which are chemically stable, non-irritating and miscible with water. In a nutshell, PEG 6000 contributes lower water solubility to suppository when compared to PEG 1000.
Different ratio of the PEGs will determine the hardness of the suppositories. With high ratio of PEG 6000 relative to PEG 1000, the suppositories will be harder, brittle and not easily dissolved by the touch of fingertips. Besides, the rate of dissolution or release of drug is lower as the formulation contents more of high melting point PEG 6000. The drug will be considered having sustained-released formulation. This is vice versa if the ratio of PEG 6000 is less than PEG 1000.
5.    Conclusion

In conclusion, suppository mould with PEG before preparing medicated suppositories was calibrated. Total weight of suppositories was determined and average mass for 1 suppository, 1.1132g was calculated.  Besides that, the effects of different compositions of PEG were determined based on the physical characteristics of suppositories. The effect of different compositions of PEG was determined by observing the time for suppositories melted in the water bath.



6.    References










Comments

Post a Comment