1. Introduction
Suppositories
are solid dosage forms of various sizes, appearance (shapes) and weights
intended for administration by rectal route where they melt, soften or dissolve
to exert their effect. They are capable of being easily inserted into the
intended orifice without causing undue distention.
The suppository
usually composed of a medicament incorporated (dissolved or suspended) in a
suppository base, this medicament may be intended for retention within the
cavity for localized drug effect or to be absorbed for the exertion of systemic
effect. For example, rectal localized action such as relief of constipation,
pain, itching and inflammation associated with hemorrhoid conditions.
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 (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.
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.
2. Objectives
· To calibrate suppository mould with PEG
before preparing medicated suppositories.
·
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
10 g of the
following proportions of PEG 1000 and PEG 6000 were used for this exercise.
|
Ingredients
|
Percentage
|
Weight Basis
|
|
PEG 1000
|
60%
|
6g
|
|
PEG 6000
|
40%
|
4 g
|
The mold was
calibrated with PEG suppository base:
1. A clean and
dry mold was prepared.
2. 6g of PEG
1000 were melted on a hot plate and mixed with 4g of PEG 6000.
3. The mixture was
removed from the heat and allowed to cool before pouring into the mold.
4. The cavities
in the mold were overfilled. It was put at the room temperature to become solid
form.
5. The excess was
removed carefully 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.
3.3.2 Preparation
of paracetamol suppositories
1. A saturated
stock solution of paracetamol was prepared by adding 10 g of paracetamol in 5
mL distilled water.
2. The following
paracetamol suppositories (10 g) were prepared using the formulation below:
|
Suppositoy
|
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 hot plate, then, the heat was reduced and the other PEG was
mixed in.
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. It was put at the room temperature to become solid
form.
6. The excess
was removed carefully with a hot spatula; then the suppositories were removed
from the mold.
7. The shape,
texture and color of the suppositories were observed and recorded.
8. Each of the
suppositories were 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.
4.
Results
Part
3.3.1
|
No of mold
|
1
|
|
Total weight for 6 suppositories (g)
|
6.0708
|
|
Average weight for 1 suppositories (g)
|
6.0708/6 = 1.0118
|
Part
3.3.2
|
Suppository
|
Shape
|
Texture
|
Colour
|
|
I
|
Bullet
|
Soft, greasy
|
Clear white
|
|
II
|
Bullet
|
Hard.
smooth, slightly greasy
|
Cloudy white
|
|
III
|
Bullet
|
Hard,
smooth, less greasy
|
White
|
|
Amount
of PEG 6000 (g)
|
0
|
3
|
9
|
|
Time
(mins)
|
7.30
|
5.25
|
3.08
|
5. Discussion
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 amount 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. There are often slight
differences between molds and even in the cavities within a mold. Dosage errors
may occur which are under dose and overdose. Therefore after calibration with
the base, we can determine the correct amount of active compound in the
suppositories produced with 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
|
Bullet-shaped
|
Softer, most greasy
|
Most transparent, opaque
|
|
II
|
6
|
3
|
Bullet-shaped
|
Soft, greasy
|
Translucent white
|
|
III
|
0
|
9
|
Bullet-shaped
|
Hard, least greasy
|
Clear white
|
All the suppositories are in
bullet-shaped as they are put inside the same suppositories moulds.
As the active ingredient used is Paracetamol
which is white in color, so the suppositories are all in white colour but
different in the transparency. The suppositories I containing only PEG 1000 and
Paracetamol solution are Most transparent and opaque in color, the suppositories II containing a mixture of PEG 1000,
6000 and Paracetamol solution are translucent white while the suppositories III
made of only PEG 6000 are in clear white color. This is due to increasing
amount of PEG 6000 and increasing amount of PEG 1000 used. PEG 1000 is white
paste which is opaque and PEG 6000 is white flake which is slightly clear.
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. 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. More of intra-molecular and inter-molecular
hydrogen bonds are formed between PEG molecules, thus increasing the overall
structure strength.
On the other hand, greasiness of the suppositories are related to the amount
and effect of PEG 1000, which is considered more hydrophobic than PEG 6000.
Suppositories I is the most greasy while suppositories III is the least greasy.
PEG 1000 is less hydrophilic and has more lipophilic property. Therefore, when
the amount of PEG 1000 decreases 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 more greasy suppositories.
3) Graph of the time required to melt the
suppository vs. the amount of PEG 6000 in the formulation.
|
Amount of PEG 6000 (g)
|
0
|
3
|
9
|
|
Time needed for the suppositories to melt (min)
|
38.36
|
42.45
|
55.57
|
The
graph above shows the time needed for the suppository to melt vs. the amount of
PEG 6000 in the formulation. The time required for the suppository to melt
increases as the amount of PEG 6000 increases in the formulation. This is
because when the PEG 6000 was not added in the formulation, the time needed for
the suppository to melt was 38.36 minutes whereas when 3g of PEG 6000 was
added, the time needed to melt the suppository increased to 42.45 minutes.
Besides, when 9g of PEG 6000 was used, the time required for the suppository to
melt was even longer which was 55.57 minutes.
In
the experiment, at constant room temperature of 37
the
suppository III with the highest amount of PEG 6000 needs the longest time to
melt whereas suppository I with the lowest amount of PEG 6000 needs the
shortest time to melt. This is due to the increased content of PEG 6000 in the
suppository increases its insolubility in the water and hence the time required
to dissolve in water.
the
suppository III with the highest amount of PEG 6000 needs the longest time to
melt whereas suppository I with the lowest amount of PEG 6000 needs the
shortest time to melt. This is due to the increased content of PEG 6000 in the
suppository increases its insolubility in the water and hence the time required
to dissolve in water.
Although
the theory regarding the time needed for the suppository to melt which depends
on the amount of PEG 6000 was proven right through the experiment, but the
results obtained were inaccurate. This is because the time after the
suppositories started to melt were taken rather than the time when the
suppositories started to melt.
4)
Describe function(s) of each ingredients used in the suppository formulation.
The ingredients used in preparing
paracetamol suppository formulation are paracetamol, polyethylene glycol (PEG),
distilled water and liquid paraffin.
Paracetamol is the main active
ingredient in the paracetamol suppository formulation where it has a major role
in giving the required therapeutic effect in the body of the patients. It is
also used as an analgesic and antipyretic medication.
Polyethylene glycol (PEG) is often
used as an excipient in pharmaceutical formulations as the PEG polymers are
water miscible type of bases. The PEGs used in the experiment are PEG 1000 and
PEG 6000. Both PEG 1000 and PEG 6000 are water-soluble carrier bases where they
increase the effective dispersion and delivery of the drugs through rectal
route by diffusing out from PEG as it degrades. The difference in the
properties such as the molecular weight of PEG 1000 and PEG 6000 affects the
physical properties of the drug such as its melting point, hardness,
smoothness, greasiness and time taken for it to melt at body temperature. PEG
6000 has higher molecular weight than PEG 1000. The higher the molecular weight
of PEG, the harder the suppository and the longer its retention time in the
body. High amount of PEG 6000 causes the suppository to solidify faster, become
harder than the one produced with PEG 1000 and have sustained release besides
affecting the rate of absorption of suppository into the body.
Besides, distilled water was used to
dissolve paracetamol in preparing saturated stock solution of paracetamol.
Liquid paraffin was also used to lubricate the suppository mold. The solidified
suppository was able to be taken out easily from the mold by lubricating the
mold.
5.
Conclusion
The physical characteristic of suppositories can
be affected by the different composition of base. It can be observed through
their physical appearance, hardness, greasiness and ease of melting. Suppository
mould was calibrated with 6g of PEG 1000 and 4g of PEG 6000 before preparing
medicated suppositories. Different amount of PEG 6000 will also affect the time
needed for the suppository to melt in body fluid. Hence influencing the rate of
release of drug from the suppositories.
6.
References
