THE EFFECT OF DIFFERENT AMOUNT OF PEG ON THE PHYSICAL CHARACTERISTICS OF SUPPOSITORY
UNIVERSITI KEBANGSAAN MALAYSIA
LAB REPORT 1
THE EFFECT OF DIFFERENT AMOUNT OF PEG ON PHYSICAL CHARACTERISTICS OF SUPPOSITORY
DEVELOPMENT OF PHARMACEUTICAL PRODUCTS II
(NFNF2283)
2019-2020 SESSION
GROUP: 2
Student’s Name : Janie Sia Phui Jeng (A167796)
Ainul Syahirah Binti Sulaiman (A167586)
Nurul Nazira binti Husin (A169005)
Nadyatul Allisya binti Himran (A168304)
Experiment Date : 5th. March 2020
Submission Date : 5th. April 2020
Lecturer’s Name : PM Dr. Haliza Binti Katas
SEMESTER II, SESSION 2019-2020
FACULTY OF PHARMACY
1.0 : TITLE
The Effect of Different Amount of PEG on the Physical Characteristics of Suppository
The Effect of Different Amount of PEG on the Physical Characteristics of Suppository
2.0 : 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.
3.0 : INTRODUCTION
A suppository is a solid dosage form that is inserted into the rectum (rectal suppository), vagina
(vaginal suppository), or urethra (urethral suppository), where it melts, softens or dissolves and
exerts local or systemic effects. Suppositories are used for retention within the cavity for localized
drug effect or to be absorbed for the exertion of systemic effect. They come in various sizes and
shapes, but they are usually narrowed at one end. They are capable of being easily inserted into
the intended orifice without causing undue distention. Suppositories are sometimes preferred over
oral drug administration because they skip first pass metabolism, reaches site of action with enhanced
bioavailability due to the prolonged drug action that can be achieved. Thus, a lower dose of medication
is required and it can reduce systemic toxicity. Moreover, patients that experience gastric irritation
through oral drug delivery can administer drugs using suppositories which can avoid severe vomiting
and nausea. Besides, suppositories are indicated for rectal localized action such as relief of constipation,
pain, itching and inflammation associated with hemorrhoid conditions.
A suppository normally consists of a medicament incorporated (dissolved or suspended) in a
suppository base. There are many types of bases available to be incorporated with the active
ingredient which is the drug. Suppository bases may be conveniently classified based on their
composition and physical properties which are oleaginous (fatty) bases and water soluble bases
available. Oleaginous bases include theobroma oil and synthetic triglyceride mixtures. Theobroma
oil or cocoa butter is used as a suppository base because it fulfills the requirements of an ideal base in
large measure. Theobroma oil melts into a bland and non-irritating oil at body temperature. On the
other hand, synthetic triglycerides consist of hydrogenated vegetable oils. Their advantage over
theobroma oil is that they do not exhibit polymorphism. As for the water soluble or water miscible
bases, they include glycerinated gelatin or the polyethylene glycol (PEG) polymers. Glycerinated
gelatin suppositories are translucent, resilient, gelatinous solids that tend to dissolve or disperse slowly
in mucous secretions to provide prolonged release of active ingredients. Polyethylene glycol (PEG)
polymers are commonly used as suppository bases in recent years due to their many desirable properties.
They are chemically stable, non-irritating, miscible with water and mucous secretions, and can be easily
formulated by compression or molding, in a wide range of hardness and melting point. In addition, they
do not melt at body temperature which is similar to glycerinated gelatin but dissolve to provide a more
prolonged release compared to theobroma oil. 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.
A suppository is a solid dosage form that is inserted into the rectum (rectal suppository), vagina
(vaginal suppository), or urethra (urethral suppository), where it melts, softens or dissolves and
exerts local or systemic effects. Suppositories are used for retention within the cavity for localized
drug effect or to be absorbed for the exertion of systemic effect. They come in various sizes and
shapes, but they are usually narrowed at one end. They are capable of being easily inserted into
the intended orifice without causing undue distention. Suppositories are sometimes preferred over
oral drug administration because they skip first pass metabolism, reaches site of action with enhanced
bioavailability due to the prolonged drug action that can be achieved. Thus, a lower dose of medication
is required and it can reduce systemic toxicity. Moreover, patients that experience gastric irritation
through oral drug delivery can administer drugs using suppositories which can avoid severe vomiting
and nausea. Besides, suppositories are indicated for rectal localized action such as relief of constipation,
pain, itching and inflammation associated with hemorrhoid conditions.
A suppository normally consists of a medicament incorporated (dissolved or suspended) in a
suppository base. There are many types of bases available to be incorporated with the active
ingredient which is the drug. Suppository bases may be conveniently classified based on their
composition and physical properties which are oleaginous (fatty) bases and water soluble bases
available. Oleaginous bases include theobroma oil and synthetic triglyceride mixtures. Theobroma
oil or cocoa butter is used as a suppository base because it fulfills the requirements of an ideal base in
large measure. Theobroma oil melts into a bland and non-irritating oil at body temperature. On the
other hand, synthetic triglycerides consist of hydrogenated vegetable oils. Their advantage over
theobroma oil is that they do not exhibit polymorphism. As for the water soluble or water miscible
bases, they include glycerinated gelatin or the polyethylene glycol (PEG) polymers. Glycerinated
gelatin suppositories are translucent, resilient, gelatinous solids that tend to dissolve or disperse slowly
in mucous secretions to provide prolonged release of active ingredients. Polyethylene glycol (PEG)
polymers are commonly used as suppository bases in recent years due to their many desirable properties.
They are chemically stable, non-irritating, miscible with water and mucous secretions, and can be easily
formulated by compression or molding, in a wide range of hardness and melting point. In addition, they
do not melt at body temperature which is similar to glycerinated gelatin but dissolve to provide a more
prolonged release compared to theobroma oil. 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.
4.0 : APPARATUS AND MATERIALS
4.1 : APPARATUS
4.2 : MATERIALS:
5.0 : EXPERIMENTAL PROCEDURES
Calibration of Suppository Molds with PEG Base
For this calibration exercise, 10 g of the following proportions of PEG 1000 and PEG 6000 were used.
For this calibration exercise, 10 g of the following proportions of PEG 1000 and PEG 6000 were used.
To calibrate the mold with PEG suppository base:
1. A clean and dry mold was prepared without lubricant.
2. PEG 1000 was melted on a hot plate. Then, the heat was reduced and the other PEG was mixed in.
3. The mixture was removed from the heat and it was allowed to cool before pouring into the mold.
4. The cavities in the mold were overloaded and let stand at room temperature until solid.
5. 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.
Preparation of paracetamol suppositories
1. Saturated stock solution of paracetamol was prepared by adding 0.1 g of paracetamol in 5 mL distilled water.
2. The following paracetamol suppository (10 g) was prepared using the formulation below:
3. One type of PEG was melted on a hot plate, then, the heat was reduced and the other was mixed in PEG.
4. The mixture was removed from the heat and allowed to cool before pouring into the mold.
5. The cavities in the mold were overfilled. Let stand at room temperature until solid.
6. 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 37 degree Celsius) and then, the beaker was put into a water bath (37 degree Celsius).
at 37 degree Celsius) and then, the beaker was put into a water bath (37 degree Celsius).
9. The time for the suppositories to melt was recorded.
4.0 : Results
Experiment 1 :
The total weight of suppositories and average weight of each suppository :
Experiment 2 :
Shape, hardness, greasiness and colour of the suppositories :
Indicator:
+ Low
++ Medium
+++ High
Time taken for the suppositories of variable amount of PEG 6000 to melt :
5.0 : Discussion
- Describe the importance of calibrating suppository mould before preparing medicated suppository.
Suppository moulds are calibrated in terms of the weight of Theobroma Oil BP each mould will contain.
important to recalibrate the mould. This is because, different base will usually have different density.
So, although each suppository will have the same volume (size) according to the opening of the mould,
but its weight varies according to the type of base used. Although most of the synthetic fats have been
formulated to match the density of Theobroma Oil, however, this is not the case for all synthetic bases.
The importance of calibrating suppository mould is to ensure an accurate dose of drug is delivered when
patients take the suppository. For the active ingredient in the drug to produce therapeutic effect, it is
important to deliver the drug at its therapeutic concentration. Anything less or more than the therapeutic
concentration will cause underdosing or overdosing respectively which will affect the safety and efficacy
of the product. Therefore, calibration is important to ensure accurate quantity of medicament is delivered.
- Compare the physical appearance of the suppositories that are formed and discuss.
amount of bases used. Suppository I contains 90% of PEG 1000 and no PEG 6000 is added. Suppository
II contains 60% of PEG 1000 and 30% of PEG 6000 whereas Suppository III contains 90% of PEG 6000
and no PEG 1000. Therefore, it is proven that the difference in physical appearance between these three
suppositories are because of the different type and amount of suppository bases used.
Firstly, in terms of shape, all three suppositories are bullet-shaped and this is due to the shape of the mould
we used. Next, we can see that the hardness of the suppository formed is inversely proportional to the
concentration of PEG 1000 used and is directly proportional to the amount of PEG 6000. Suppository I
with the lowest PEG 6000 have the lowest hardness followed by Suppository II with medium hardness
and Suppository III which contain the highest amount of PEG 6000 is relatively the hardest among these
three suppositories. Theoretically, the number indicates the molecular weight of the PEG base used. As the
molecular weight of PEG increases, this will make the suppository more solid because there will be more
hydroxyl groups present as we increase the concentration of PEG 6000. As a result, more hydrogen bonds
will be formed which will make the suppository harder.
Similarly, Suppository III with the highest PEG 6000 should have a higher melting point compared to
Suppository I that does not contain PEG 6000 at all, and Suppository II that has only 30% PEG 6000.
There are five ingredients that are used in this experiment which are polyethylene glycol (PEG) 1000,
Furthermore, in terms of greasiness we can see that Suppository I with the highest content of PEG
1000 is the most greasy, followed by Supposisitory II with medium greasiness and Suppository III with the
lowest PEG 1000 content is relatively the least greasy. Greasiness is affected by hygroscopicity and
hydrogopicity is affected by molecular weight of the PEG baase used. Since PEG 1000 has lower
molecular weight than PEG 6000, therefore it will have a more hygroscopic suppository. So, when we use
more PEG 1000 rather than PEG 6000, a more greasy wax like suppository will be formed due to its
increase in hygroscopicity. If we use more PEG 6000 as in Suppository III, we will have a less greasy
suppository as it is less hygroscopic.
1000 is the most greasy, followed by Supposisitory II with medium greasiness and Suppository III with the
lowest PEG 1000 content is relatively the least greasy. Greasiness is affected by hygroscopicity and
hydrogopicity is affected by molecular weight of the PEG baase used. Since PEG 1000 has lower
molecular weight than PEG 6000, therefore it will have a more hygroscopic suppository. So, when we use
more PEG 1000 rather than PEG 6000, a more greasy wax like suppository will be formed due to its
increase in hygroscopicity. If we use more PEG 6000 as in Suppository III, we will have a less greasy
suppository as it is less hygroscopic.
Finally, in terms of colour, all three suppositories are white in colour due to the colour of Paracetamol
active ingredient incorporated in the base is white. However, we can observe difference in the intensity
of white colour. Suppository 1 with the least amount of PEG 6000 is the least opaque, followed by
Suppository II with medium opacity and finally Suppository III is relatively the most opaque due to the
highest PEG 6000 content. This is because the colour of the final product is affected by the molecular
weight of the PEG base used. As we increase the amount of PEG 6000, which is a base with higher
molecular weight compared to PEG 1000, a more opaque final product is formed. However, in
Suppository I, since we only use PEG 1000 which is a base with relatively lower molecular weight, a
transparent white final product is formed.
active ingredient incorporated in the base is white. However, we can observe difference in the intensity
of white colour. Suppository 1 with the least amount of PEG 6000 is the least opaque, followed by
Suppository II with medium opacity and finally Suppository III is relatively the most opaque due to the
highest PEG 6000 content. This is because the colour of the final product is affected by the molecular
weight of the PEG base used. As we increase the amount of PEG 6000, which is a base with higher
molecular weight compared to PEG 1000, a more opaque final product is formed. However, in
Suppository I, since we only use PEG 1000 which is a base with relatively lower molecular weight, a
transparent white final product is formed.
- Plot a graph of time required to melt the suppository vs. the amount of PEG 6000 in the
Based on the results, it can be observed that Suppository III takes the longest time to melt
compared to Suppository II and I. This is because Suppository III contains the highest amount
of PEG 6000.
Two types of bases were used during the experiment: PEG 1000 and PEG 6000. Polyethylene
glycol 6000 (PEG) is a polyether compound. The structure of PEG is:
glycol 6000 (PEG) is a polyether compound. The structure of PEG is:
HO-CH2-(CH2-O-CH2-)n-CH2-OH
PEG 6000 indicates the average molecular weight of the specific PEG at 6000. As we know, one of the
factors that affect the melting point of an organic compound is its molecular weight. For substances of
similar structure and comparable polarity like PEG1000 and PEG6000, intermolecular attractive forces
increase with increasing molecular weight. A higher intermolecular attractive force within the substance
will need a higher amount of energy in order to break off the forces and initiate its melting. Hence leading
to the conclusion that a substance with higher molecular weight will have a higher melting point.
factors that affect the melting point of an organic compound is its molecular weight. For substances of
similar structure and comparable polarity like PEG1000 and PEG6000, intermolecular attractive forces
increase with increasing molecular weight. A higher intermolecular attractive force within the substance
will need a higher amount of energy in order to break off the forces and initiate its melting. Hence leading
to the conclusion that a substance with higher molecular weight will have a higher melting point.
Similarly, Suppository III with the highest PEG 6000 should have a higher melting point compared to
Suppository I that does not contain PEG 6000 at all, and Suppository II that has only 30% PEG 6000.
- Describe function(s) of each ingredient used in the suppository formulation.
There are five ingredients that are used in this experiment which are polyethylene glycol (PEG) 1000,
polyethylene glycol (PEG) 6000, paracetamol, liquid paraffin and distilled water. The PEG 1000 and
6000 are commonly used as a suppository base. They are classified as hydrophilic bases where they
enhance the solubility of therapeutic agents, do not allow bacterial growth on suppository and provide
prolonged action. They can dissolve in the body of the patient in the presence of fluid. PEG 1000 has
smaller molecular weight compared to PEG 6000. Increased molecular weight will decrease the
solubility in the water and solvent therefore increase the melting point. Paracetamol acts as the active
ingredients and functions as an anti-pyretic and analgesic. Liquid paraffin acts as a lubricant to facilitate
the removal of the suppositories from the mould. Other than that, distilled water acts as solvent to
dissolve paracetamol powder.
6.0 : Conclusion
From Activity 1, the average weight of one suppository is 1.0983g, which is 0.0983g heavier than the
expected weight of 1g. This is because PEG has a higher density compared to Theobroma oil. The density
of PEG is 1.126 g/mL at 20 °C whereas the density of Theobroma oil is 0.860g/mL at room temperature.
Since density is directly proportional to the weight of suppository base, we can see that when we use PEG
base which is denser than theobroma oil, an increase in the average weight of suppository base is observed
although both have the same volume as we are using the same suppository mould.
From Activity 2, the shape of suppository formed will depend on the shape of the mould used. In terms
of hardness, hardness of the final product is directly proportional to the amount of PEG 6000 used and
inversely proportional to the amount of PEG 1000 used. Next, in terms of greasiness, greasiness of the
final product is directly proportional to the amount of PEG 1000 and inversely proportional to the
amount of PEG 6000 used. Next in terms of colour, the colour of final product depends on the colour of
the active ingredient added to the otherwise white base. However, the opacity of the suppository is
directly proportional to the amount of PEG 6000 used and inversely proportional to the amount of PEG
1000. In terms of time taken to melt the suppository, the higher the amount of PEG 6000 used, the
higher the melting point and therefore a longer time is required to melt the suppository.
From Activity 1, the average weight of one suppository is 1.0983g, which is 0.0983g heavier than the
expected weight of 1g. This is because PEG has a higher density compared to Theobroma oil. The density
of PEG is 1.126 g/mL at 20 °C whereas the density of Theobroma oil is 0.860g/mL at room temperature.
Since density is directly proportional to the weight of suppository base, we can see that when we use PEG
base which is denser than theobroma oil, an increase in the average weight of suppository base is observed
although both have the same volume as we are using the same suppository mould.
From Activity 2, the shape of suppository formed will depend on the shape of the mould used. In terms
of hardness, hardness of the final product is directly proportional to the amount of PEG 6000 used and
inversely proportional to the amount of PEG 1000 used. Next, in terms of greasiness, greasiness of the
final product is directly proportional to the amount of PEG 1000 and inversely proportional to the
amount of PEG 6000 used. Next in terms of colour, the colour of final product depends on the colour of
the active ingredient added to the otherwise white base. However, the opacity of the suppository is
directly proportional to the amount of PEG 6000 used and inversely proportional to the amount of PEG
1000. In terms of time taken to melt the suppository, the higher the amount of PEG 6000 used, the
higher the melting point and therefore a longer time is required to melt the suppository.
7.0 : References
1. Marriott JF, Wilson KA, Langley CA, Belcher D. Pharmaceutical compounding and dispensing. 2nd Revised Edition.
London: Pharmaceutical Press; 2012.
2. Niazi S. Handbook of pharmaceutical manufacturing formulations . 2nd ed. Vol. 4. Boca Raton: CRC Press; 2009.
3. Suppositories [Internet]. Pharmaceuticals. [cited 2020Apr1]. Available from: https://pharmaceutical.basf.com/global/en/drug-formulation/dosage-forms/suppositories.html
4. Eldridge, J. E., & Ferry, J. D. 1954. Studies of the Cross-linking Process in Gelatin Gels. III. Dependence of Melting Point on Concentration and Molecular Weight. The Journal of Physical Chemistry, 58(11), 992–995. https://sci-hub.tw/10.1021/j150521a013 [3 April 2020].
1. Marriott JF, Wilson KA, Langley CA, Belcher D. Pharmaceutical compounding and dispensing. 2nd Revised Edition.
London: Pharmaceutical Press; 2012.
2. Niazi S. Handbook of pharmaceutical manufacturing formulations . 2nd ed. Vol. 4. Boca Raton: CRC Press; 2009.
3. Suppositories [Internet]. Pharmaceuticals. [cited 2020Apr1]. Available from: https://pharmaceutical.basf.com/global/en/drug-formulation/dosage-forms/suppositories.html
4. Eldridge, J. E., & Ferry, J. D. 1954. Studies of the Cross-linking Process in Gelatin Gels. III. Dependence of Melting Point on Concentration and Molecular Weight. The Journal of Physical Chemistry, 58(11), 992–995. https://sci-hub.tw/10.1021/j150521a013 [3 April 2020].
Comments
Post a Comment