OBJECTIVES
1. To study and examine the effects of different formulation of ointment on the physical characteristics of formed ointment.
2. To evaluate the rate of drug release for different formulations of ointment.
INTRODUCTION
Emulsifying ointment is a
mixture of paraffin oils (white soft and liquid parafin) and emulsifying wax. It is a greasy moisturiser that provides a layer of oil on the surface of the
skin to prevent water evaporating from the skin surface. In medical terms, an
ointment is defines as a homogeneous, viscous, semi-solid preparation with a
high viscosity for external application only. It contain medicated ingredients
which serve a protective, therapeutic, or prophylactic purpose when applied on
the skin or mucous membranes.
Theoretically, according to the British
Pharmacopoeia (BP), the best ointment formulation contains emulsifying wax 30%
w/w which render the
ointment to be more smooth and light in its consistency
, white soft paraffin 50% w/w which acts
as an emollient and a heavy
moisturizer while liquid paraffin 20%
w/w for reliever of dryness and irritation by lubricating and
protecting the surface. Therefore, by altering the the
proportions of paraffin and wax in the ointment may vary the
consistency of ointment and affect the rate of drug release of drug (
Acetylsalicyclic acid) which can be measure using UV spectrometer.During the
experiment, the methods of preparation of ointments
included levigation,trituration and fusion. In levigation, finely subdivided
insoluble medicaments are evenly distributed by grinding with a small amount of
the base, while in fusion, the ingredients are melted together in descending
order of their melting points and stirred to ensure homogeneity.
APPARATUS
- measuring cylinder
- weighing boat
- 100ml beaker
- heater
- a set of slap & spatula
- set of mortar & pestle
- dialysis bag (10cm)
- 2 threads
- glass rod
- water-bath
- set of pipette (5ml) and a pipette-bulb
- plastic cuvette
- spectrophotometer UV/Vis.
MATERIALS
- emulsifying wax
- white soft paraffin
- liquid paraffin
- acetylsalicylic acid
- distilled water
PROCEDURES
1. 50g of Emulsifying Ointment is prepared by using the formula following:
Emulsifying Ointment |
Group |
Material (g) |
Total (g) |
||
Emulsifying Wax |
White Soft Paraffin |
Liquid Paraffin |
|||
I |
1,5 |
21 |
25 |
4 |
50 |
II |
2,6 |
17 |
25 |
8 |
50 |
III |
3,7 |
13 |
25 |
12 |
50 |
IV |
4,8 |
9 |
25 |
16 |
50 |
2. 5g of ointment formed is weighed. The ointment is put in the weighing boat and labeled. The texture, clarity and the colour of the ointment formed are discussed and compared.
3. 1.5g of Acetylsalicylic acid is weighed
and grinded with mortar and pestle.
4. The weighed amount of acetylsalicylic acid is mixed with 30g of ointment
weighed by using levigation method.
5. Then, the Acetylsalicylic acid ointment is filled into the
dialysis beg. Both end of the beg are tied properly as shown as below.
6. The dialysis beg is
put into a 100mL beaker with 50mL of distilled water which is been heated on 370C.
7. With the interval of each 5 minutes, 3-4mL of the distilled water is
pipetted out. The release of acetylsalicylic acid from the ointment is
determined by using UV-visible spectrometer. Distilled water is stirred before
the taking the sample.
RESULTS AND DISCUSSION
1.
Observe and explain the physical differences of the ointment that
are produced.
In this experiment, we had prepared four
emulsifying ointment of 50g which each of them consist of difference amount of
material. Emulsifying ointment 1 consist of 21g of emulsifying wax, 25 white
paraffin and 4g liquid paraffin. Emulsifying ointment 2 consist of 17g
emulsifying wax, 25g white paraffin and 8g liquid paraffin. Emulsifying
ointment 3 consist of 13g emulsifying wax, 25g white soft paraffin and 12g
liquid paraffin. Then lastly is the emulsifying ointment 4, it consist of 9g
emulsifying wax, 25g white soft paraffin and 16g liquid paraffin.
When observing in term of spreadability,
emulsifying ointment 4 is the most spreadable than followed by emulsifying
ointment 3, 2 and 1 which is the most less spreadable. Same with the greasy, the emulsifying
ointment 3 is the most greasy then followed by 3,2 and 1. Next, in term of
hardness, the emulsifying ointment 1 is the most hardest the followed by
ointment 2, 3 and 4 the most soft.
From the observation it shows that we can
compare difference composition of the ointment based on this three component.
It is shows that when the greasiness and the spreadability is increase, the
hardness is decrease.
These three component can be cause by the
amount of the paraffin oil that are used. High amount of paraffin oil, will increase the
greasiness and spreadability but decrease in hardness. Therefore to form an
ideal ointment, we need to balance the amount of the emulsifying wax and
paraffin oil.
Time (min) |
0 |
5 |
10 |
15 |
20 |
25 |
30 |
Average UV Absorption at 300nm |
0.025 |
0.450 |
0.492 |
0.527 |
0.553 |
0.581 |
0.590 |
Based on the graph, the UV absorption from the water
sample increased steadily over time. Therefore, on the graph, a linear line is
obtained. The ointment is made with 21g of emulsifying wax, 25g white soft
paraffin, 4g liquid paraffin and 1.5g of acetylsalicylic acid. Since the
ointment was made with higher amount of emulsifying wax than the liquid
paraffin, the ointment came out harder and has high viscosity (in liquid form
during heating) based on the physical appearance.
Depending on partition coefficient, for drug that is very soluble in the
vehicle, the tendency for the drug to leave the vehicle is small hence the rate
of drug releasing will be slow. Acetylsalicylic acid is a weakly acidic drug
and slightly soluble in water. The bases that aids in the releasing of the
hydrophilic drugs are bases that are made from fatty bases or hydrocarbon
bases. Emulsifying wax, liquid paraffin and white soft paraffin are hydrocarbon
bases. Therefore, they provide good rate of drug releasing from the ointment.
Since acetylsalicylic acid is a polar drug, it diffuses easily from the plastic
bag towards the water in the beaker. The steady rate of releasing drug from the
ointment and also combined with the easy diffusion of the drug across the
plastic bag, causes a constant increasing of UV absorption over time that is
shown in the graph (linear graph).
3. Graph of UV
absorption against time is plotted for ointment formulation which contains
different composition. Compare and discuss the results.
Time (min) |
Average UV Absorption at 300nm ( x ± SD ) |
||||||||
0 |
5 |
10 |
15 |
20 |
25 |
30 |
|||
Emulsifying Ointment |
I |
Group 1 |
0.030 |
0.068 |
0.076 |
0.095 |
0.112 |
0.128 |
0.157 |
Group 5 |
0.015 |
0.056 |
0.056 |
0.094 |
0.109 |
0.121 |
0.172 |
||
Average |
0.023 |
0.062 |
0.066 |
0.095 |
0.111 |
0.125 |
0.165 |
||
SD |
0.0106 |
0.0085 |
0.0141 |
0.0007 |
0.0021 |
0.0049 |
0.0106 |
||
II |
Group 2 |
0.025 |
0.450 |
0.492 |
0.527 |
0.553 |
0.581 |
0.590 |
|
Group 6 |
0.073 |
0.120 |
0.140 |
0.180 |
0.243 |
0.263 |
0.286 |
||
Average |
0.049 |
0.285 |
0.316 |
0.354 |
0.398 |
0.422 |
0.438 |
||
SD |
0.0339 |
0.2333 |
0.2489 |
0.2454 |
0.2192 |
0.2249 |
0.2150 |
||
III |
Group 3 |
0.035 |
0.042 |
0.046 |
0.055 |
0.058 |
0.062 |
0.070 |
|
Group 7 |
0.039 |
0.040 |
0.113 |
0.101 |
0.162 |
0.192 |
0.239 |
||
Average |
0.037 |
0.041 |
0.080 |
0.078 |
0.110 |
0.127 |
0.155 |
||
SD |
0.0028 |
0.0014 |
0.0474 |
0.0325 |
0.0735 |
0.0919 |
0.1195 |
||
IV |
Group 4 |
0.063 |
0.121 |
0.212 |
0.224 |
0.235 |
0.294 |
0.331 |
|
Group 8 |
0.100 |
0.183 |
0.224 |
0.221 |
0.222 |
0.240 |
0.311 |
||
Average |
0.082 |
0.152 |
0.218 |
0.223 |
0.229 |
0.267 |
0.321 |
||
SD |
0.0262 |
0.0438 |
0.0085 |
0.0021 |
0.0092 |
0.0382 |
0.0141 |
||
Based on the graph above, the average UV
absorption for each formulation increases with time. This is due to the
increase in the concentration of acetylsalicylic acid in the beaker. In every
interval of 5 minutes, 3 to 4ml of aliquot were taken from the solution
surrounding the dialysis bag in the beaker rendering a progressive decrease in
amount of solution in the beaker. On the other hand, the active ingredient in
the ointment was being released into the solution at the surrounding from time
to time. Thus, the concentration of the active ingredient- acetylsalicylic acid
increases progressively which is indicated by an increase in the average UV absorption.
In an
overall, the standard deviation of all four formulation show inconsistency. For
instance, there is a sharp decrease in standard deviation of formulation I at
20 minutes. Besides, there is a great increase in standard deviation of
formulation II between 0 and 5 minutes, but quite a uniform value after 5
minutes. This can be explain that the result of formulation II obtained is
consistent among the two groups that had been worked on that formulation. Next,
for formulation III, the standard deviation of o and 5 minutes is quite small,
but increase drastically after 5
minutes. As for formulation IV, the value of standard deviation of this
formulation also show a great difference in every 5 minutes interval. This
shows that there might be some errors occur in one of the groups.
From
the graph, ointment IV shows the smallest gradient among the 4 slopes. This
result is inaccurate as the result that we expect is ointment IV should have
the highest reading of released acetylsalicylic acid. This is due to the
presence of low emulfsying wax that causes the matrix not fine enough to trap
liquid paraffin and soft paraffin. Incomplete matrix causes the emulsifying
ointment formed to be unstable and hence it cannot disperse evenly. As a
result, this leads to the hydrophilic ointment to diffuse into the distilled
water through the membrane.
Drug diffusion of emulsifying ointment is
affected by the formulation of emulsifying wax and liquid paraffin.
Theoretically, ointment IV should have the highest reading of released
acetylsalicylic acid followed by emulsifying ointment III, II and the drug diffusion
of emulsifying ointment I is the least. This is due to the presence of low
emulfsying wax that causes the matrix not fine enough to trap liquid paraffin
and soft paraffin. Incomplete matrix causes the emulsifying ointment formed to
be unstable and hence it cannot disperse evenly. As a result, this leads to the
hydrophilic ointment to diffuse into the distilled water through the membrane.
However, with reference to the graph above, the result that we obtained is in
the following order :
The conflict in the result obtained is due to some
errors that took place. Firstly, the method of ointment preparation may affect
the rate of drug diffusion. Some groups mixed and melted all the bases together
before incorporation of acetylsalicylic acid with levigation technique.
Meanwhile, some groups melted the hard emulsifying wax only and mix with white
soft paraffin and liquid paraffin which is soft in nature using levigation
technique. Then the drug is incorporated using the same technique as well.
These may result in non-homogenous mixture of drug and bases. Drug is not
evenly distributed in the bases. Therefore, this contributes to the abnormal
rate of drug diffusion. The second error that might take place is that the outer membrane of dialysis bag may be contaminated
with the emulsifying ointment during the filling of ointment into the bag.
Thus, the rate of drug diffusion might be affected. Thirdly, there was
splitation occurred when carrying the practical. The solution from that
particular beaker may contaminated other
solutions as all the beakers shared the same water bath. Last but not least,
there is great difference in values of UV absorption between group 1 and 5
which results in large standard deviation. This probably due to different
preaparation techniques or one of the group did not stir the solution well each
time when taking out solution from the beaker.
4. The function of the
materials in the ointment. How does the different emulsifying wax and liquid
paraffin components affect the physical appearance of the ointment formed and
the release rate of the drug from the ointment?
Emulsifying wax is an emulsifying agent that is used
to make the oil droplets in ointment becomes soluble and mixable with water in
order to allow the formation of the ointment. It also allows the ointment to
have self-emulsifying property. Liquid paraffin and soft paraffin are the
hydrophobic bases of the ointment. Liquid paraffin softens the ointment formed
and reduces the viscosity of the ointment in the presence of emulsifying wax.
It increases the spreadibility and decreases the hardness of the ointment. White soft paraffin enhances the
penetration of acetylsalicylic acid through skin surface as well as the
absorption through the membrane into circulation.
From the experiment, different proportions of
materials are used to produce 50g of emulsifying ointment. High concentration
of emulsifying wax hardened the ointment while a high concentration of liquid
paraffin produces a watery, greasy, and soft ointment due to the reduced
viscosity of ointment. Therefore, higher concentration of emulsifying wax and
lower concentration of liquid paraffin produce harder and less greasy ointment
compared to lower concentration of emulsifying wax and higher concentration of liquid
paraffin in an ointment formulation.
In this formulation, the increased
concentration of emulsifying wax reduces the rate of drug released from
ointment. This is because higher amount of emulsifying wax will decrease the
drug diffusion from ointment by holding the active ingredient (acetylsalicylic
acid) tightly and thus retard the drug released. On the other hand, diffusion
rate of acetylsalicylic acid from the dialysis tube is increased in a
formulation of ointment with optimum concentration of liquid paraffin because
acetylsalicylic acid which is hydrophilic is tend to diffuse into the
surrounding distilled water. Hence, the release rate of drug is increased.
However, the diffusion rate of acetylsalicylic acid will decrease when the
concentration of liquid paraffin is beyond the optimum value. Thus, an optimum
ratio of the phases is needed to produce an ointment with good physical
property and also the drug releasing rate.
