TITLE:
The Effect Of Different Amount Of Peg On The Physical Characteristics Of
Suppository
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.
DATE
OF EXPERIMENT: 8 March 2017
INTRODUCTION
Suppositories are
solid, single dose preparations of various sizes, shapes and weights that are
suitable for rectal administration. They are capable of being easily inserted
into the intended orifice where they melt at body temperature, soften or
dissolve to produce their effect. Suppository bases usually employed are cocoa
butter, glycerinated gelatin, hydrogenated vegetable oils and polyethylene
glycol (PEG). The type of material used depends on the type of suppository, the
type of drug and the conditions in which the suppository is stored. Ideal
suppository should be stable during storage condition and exist in solid form
at room temperature; not irritate and produce inflamed sensation in body
cavity; not reacts with drugs and additives; release the medicaments readily;
melt at body temperature or dissolve or disperse in body fluids.
PEG suppository bases
and glycerinated gelatin are the most popular in the class of water soluble
bases. PEG are available in a variety of molecular weight range from the
low-molecular-weight-liquid PEG 300 to the high-molecular-weight solid PEG
8000, which can allow the individual weight to be altered to prepare a base
with specific melting point and hardness. An individual PEG can be used as a
base itself or two or more PEGs can be used in combination. The different
compositions of PEG bases used in combination can affect the physical
characteristics of the suppositories.
EXPERIMENTAL
METHOD:
APPARATUS
Analytical balance 4 x Weighing boats
1 x Suppository mould
set 4 x 50
mL beaker
Water bath at 37Oc 2 x
Glass rod
1 x Spatula
1 x 5 mL pipette and pipette bulb
Hotplate
1 x 5 mL measuring cylinder
MATERIALS
Polyethylene glycol
(PEG) 1000 Distilled
water
Polyethylene glycol
(PEG) 6000 Liquid paraffin
Paracetamol
PROCEDURES:
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 (g)
|
PEG 1000
|
60%
|
6.0
|
PEG 6000
|
40%
|
4.0
|
To calibrate the mold
with PEG suppository base:
1. A mold is cleaned
and dried without lubricating it.
2. 6g of PEG 1000 is
melt on a hot plate, then, the heat is reduced before being mixed in the other
PEG.
3. The mixture is
removed from the heat and is allowed to cool before pouring into the mold.
4. The cavities in the
mold is overfill when pouring. The mold is left stand at room temperature until
it become solid.
5. The excess is
removed carefully with a hot spatula; then the suppositories are removed from
the mold.
6. The suppositories
are weighed and the total weight is recorded. The average suppository weight is
calculated.
 |
| Preparing saturated stock of Paracetamol |
 |
| Pouring the sample into lubricated suppository case |
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 (g)
|
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 hot plate, then, the heat is reduced and mixed in the other PEG. 1g
of paracetamol stock solution is added and mixed in the mixture.
4. The mixture is
removed from the heat and is allowed it to cool before pouring into the mold.
5. The cavities is
overfilled in the mold and is let to stand at room temperature until solid.
6. The excess is
removed carefully with a hot spatula; then the suppositories are removed from
the mold.
7. The shape, texture and color of the
suppositories is observed and recorded.
8. Each of the
suppositories is put into a separate beaker or test tube containing distilled
water (10 mL and pre-warmed at 37oC) and then, the test tube is put into a
water bath (37oC).
9. The time for the
suppositories to melt is recorded.
 |
| Excess suppository is removed after its get cold |
RESULT:
Experiment 3.3.1 Calibration of Suppository
Molds with PEG Base
Mold
#
|
1
|
Total
Weight for 6 suppositories =
|
5.844g
|
Average
weight for one suppository =
|
0.974g
|
Table 3.1 Weight for suppositories
Experiment 3.3.2 Preparation of
Paracetamol Suppositories
Suppository
|
Shape
|
Texture
|
Color
|
I
|
Bullet
|
Soft,
greasy, and smooth
|
Intense
White
|
II
|
Bullet
|
Hard,
greasy, and smooth
|
White
|
III
|
Bullet
|
Hard,
less greasy, and smooth
|
White
|
Table 3.2 Characteristic of Paracetamol
Suppositories
PEG
amount (g)
|
0
|
3
|
9
|
Time
(min)
|
5.30
|
1.1
|
9.12
|
Table 3.3 Time taken for the paracetamol
suppositories to melt
DISCUSSION:
Generally, suppository preparations are
made from solid drugs dispersed in solid ingredients or base. All of the
ingredients are measured by weight. When the ingredients are mixed, melted and
poured into the suppository mould cavity, they occupy a volume in the mould
cavity. Ingredients having different densities causes the suppository to have
different weight when the same mould is used. Mould calibrations are required
to ensure accurate dose of preparations are produced. This is because the
components are measured by weight but compounded by volume.
Addition of any medicament results in the
altering of weight of the suppository. When a drug is placed in a suppository
base, it will displace an amount of base as a function of its density. If the
drug has the same density as the base, an equivalent weight of the base will be
displaced. A greater density drug will displace a proportionally smaller weight
of the base.
To calculate the volume of moulds, empty
suppositories are prepared from base material alone. In extemporaneous
preparations, the amount of base required is determined by subtracting the
volume of medicaments from the total volume of mould.
Suppository
|
I
|
II
|
III
|
Surface
|
smooth
|
smooth
|
smooth
|
Colour
|
Clear white
|
Intense white
|
Intense white
|
Texture
|
Soft and sticky
|
Moderately hard and slightly sticky
|
Hard and non-sticky
|
The
physical appearance of the suppositories is based on the ratio of PEG100 and
PEG6000. The higher percentage of PEG6000 in the suppositories, the harder the
suppositories is. Suppository I is the softest as it has the highest percentage
of PEG1000. PEG1000 has the melting point between 35 and 40 degree Celsius,
which is close to human body temperature. When it is inserted to the rectum, it
shows stickiness and melts.
Suppository
II is slightly harder and less sticky compared to suppository I due to the
combination of PEG1000 and PEG6000. The presence of PEG6000 increases the
hardness of the suppository.
Suppository III is the hardest among the three
suppositories. It is completely made of PEG6000 which has melting point between
60-63 degree celcius. It is harder to melt at body temperature and thus has a greater solid properties than
suppositories I and II
PEG is a water soluble base for suppository.
Different types of PEG have different molecular weight ranging from
2000 up to 6000. The differences in molecular weights will contribute to
differences in the solubility, freezing point and also the melting point. The
higher the molecular weight of the polyethylene glycol, the higher the melting
point of the suppositories. Therefore, high molecular weight PEG requires a
longer time to melt. PEG 6000 have higher melting point compared to PEG 1000
due to its molecular weight.
Based
on the graph above, it can be observed that the graph shows a “V” shape. When
no PEG 6000 is added, the formulation is wholly consisted of PEG 1000. The
melting point of PEG 1000 is low, which is similar to the normal human body
temperature (37°C). Hence, formulation I takes short duration to melt, which only
requires 5.3 minutes to start dissolving in the water bath. Formulation II
consists of 6 g of PEG 1000 and 3 g of PEG 6000 has melting time of 1.1 minutes.
The melting point of PEG 6000 is in the range of (56 – 630) °C. For the
formulation III, the suppository is wholly consisted of 9 g of PEG 6000. High
composition of PEG 6000 contribute to more of hydroxyl groups (-OH) that are
capable to form strong hydrogen bonds with paracetamol. Therefore, longer time is needed to break the bond in
order for the suppository to melt and release the drug. Thus,
formulation III takes the longest time, 9.12 minutes to start melting in the
water bath.
According
to the results obtained from the experiment, the average time taken for the
suppositories to melt increases as the amount of the PEG 6000 increase from 3g
to 9g. However, the time taken drops as the amount of PEG 6000 increases from
0g to 3g. These results do not conform to the theory as errors may occur during
the procedures. The suppositories may be contaminated during the compounding
process which leads to a lower melting point. Besides, inappropriate handling
and measurement of the polyethylene glycol may also affect the results.
The active ingredient of the suppository formulation is Paracetamol,
while the inactive ingredient is Polyethylene Glycol (PEG). Polyethylene Glycol acts as suppository base,
as they possess desirable properties, such as chemically stable and miscible
with water and mucous secretion. They have wide range of melting point which
results in formation of suppositories of different hardness. The difference
between the melting point of PEG1000 and PEG6000 causes different hardness of
suppositories produced. Polyethylene Glycol can be used either singly or in
combination to get product of satisfactory hardness and dissolution time.
The active
ingredient, Paracetamol is a pain reliever and fever reducer. It is usually be
used to relieve mild to moderate pain such as headaches, backache, and
menstrual pain.
CONCLUSION:
Different
composition of PEG 1000 and PEG 6000 in the suppository base mixture affects
the physical characteristics of suppository. The higher the amount of PEG 6000,
the harder, the less greasy and the higher the melting point of the
suppository.
REFERENCES:
