EXPERIMENT 1: OINTMENT
TITLE
To know the effects of different ointment formulation to the physical characteristic of the ointment and the rate of release of drug from the formulation
To know the effects of different
ointment formulation to the physical characteristic of the ointment and the
rate of release of drug from the formulation.
rate of release of drug from the formulation.
INTRODUCTION
Ointment refers to
the semisolid dosage which used for the topical application on a variety of
body surfaces. These include the skin and the mucous membranes of the eye (an
eye ointment), vagina, anus, and nose. An ointment may or may not be medicated.
It is an oily preparation containing active drug that will dissolved or
disperse homogenously in the preparation. The functions of ointment are used
for topical application and give emollient effects A good ointment has the
properties of nice texture, easy to spread onto the skin and able to release
the active ingredients.
In general,
ointment consists of active ingredient (powder or liquid) which incorporated
into the ointment base. There are four groups of ointment bases: hydrocarbon
bases, absorption bases, water-miscible bases and water-soluble phases. The
choice of a base depends upon the clinical indication for the ointment. Properties which affect choice of an ointment base include
stability, penetrability, solvent property, irritant effects and ease of
application and removal. An ointment base which can penetrate into the skin and
release the medication is an ideal base for antiseptic ointment, while an
ointment base has a poor penetrating power is ideal for a protective ointment
against moisture, air, UV lights and other external factors.
MATERIALS AND APPARATUS
Apparatus: Materials:
Weighing
instrument Emulsifying
wax
Weighing boat White
soft paraffin
100ml beaker Liquid
paraffin
Heater Acetylsalicylic
acid
1 set of
cream and spatula Distilled
water
Mortar and
pestle
Dialysis bag
(10cm)
Thread
Glass rod
Water-bath
1 set of
pipette (5 ml) and pipette-bulb
1 plastic
kuvet
Spectrophotometer
UV/Vis
PROCEDURES
1.
50g of Emulsifying Wax was prepared based on the following formulation:
Emulsifying Ointment
|
Ingredients (g)
|
Total (g)
|
||
Emulsifying wax
|
White soft paraffin
|
Liquid paraffin
|
||
I
|
21
|
25
|
4
|
50
|
II
|
17
|
25
|
8
|
50
|
III
|
13
|
25
|
12
|
50
|
IV
|
9
|
25
|
16
|
50
|
2.
5 g of the ointment formed is taken and placed into the weighing boat and
then labeled. The texture, clarity and the color of the ointment is described
and compared.
3. 1.5 g of Acetylsalicylic acid powder was incorporated into 15 g of
ointment that was prepared by the levigation technique.
4. Acetylsalicylic acid is then filled into the dialysis bag and the two sides of the bag is made sure to be tied neatly, like the diagram below:
5. The bag is placed into a beaker (250ml) filled with distilled water (100ml) which was already heated to the temperature of 37°C.
6. Every interval of 5 minutes, one aliquot sample (3 – 4 ml) was pipetted out and the release of acetylsalicylic acid from the ointment base was determined by using the spectrometer UV-visible. The distilled water is made sure to be stirred with the glass rod before the sample was taken.
1.
Compare the physical appearance of the ointment formed and give your
explanation.
Group
|
Texture
|
Clarity
|
Colour
|
Greasiness
|
Spreadability
|
Emulsifying Ointment I
|
Hardest
|
Higly Opaque
|
White
|
Least greasy
|
Very difficult
|
Emulsifying Ointment II
|
Hard
|
Opaque
|
White
|
Less greasy
|
Difficult
|
Emulsifying Ointment III
|
Soft
|
Clear
|
White
|
Greasy
|
Less Difficult
|
Emulsifying Ointment IV
|
Softest
|
Very Clear
|
White
|
Very greasy
|
Easily
|
From the experiment , we found that the the poor clarity of ointment is due to the
emulsifying wax and also the liquid paraffin presence in the ointment.The higher
the content of emulsifying wax, the harder will be the ointment. Besides that,
the higher the content of liquid paraffin, the smoother the ointment and the lesser
the turbidity. This cause it easier to be spread, and increase in it greasiness
due to increases in the liquid paraffin.
2.
Plot the graph of UV absorption against time. Give explanation.
Time (minutes)
|
UV Absorption
|
||||||||||||
0
|
5
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
|
UV Absorption at 310 nm
|
0
|
0.047
|
0.049
|
0.146
|
0.158
|
0.183
|
0.220
|
0.236
|
0.253
|
0.277
|
0.289
|
0.319
|
0.387
|
The graph above shows the relationship between the UV
absorption against time for acetylsalicylic acid ointment with Formulation III.
Generally, the UV absorption of ointment increases with time. The value of UV
absorption is correspond to the amount of acetylsalicylic acid release from
ointment in the dialysis beg into the surrounding solution in the beaker.
This
experiment demonstrated the release of the drugs from the ointment formulation
into the blood circulation in our body.
The dialysis bag serves as an excellent representation of the
phospholipid membrane bilayer and the distilled water in the beaker acts as the
blood plasma. Also, the temperature of
the system was maintained at 37oC, which represents the body
temperature. The release of the drugs from the ointment (in dialysis bag) into
the distilled water involved the diffusion mechanism. From the graph plotted, when the time
increases, the amount of the acetylsalicylic acid diffuse into the distilled
water also increases, thus results in gradual increased in the UV absorption
value as more of the UV light is being absorbed. The rate of drug release can
be calculated from the gradient of the graph.
Theoretically,
the drug concentration in the ointment is the highest in the beginning of the
experiment, and it tends to diffuse out of the ointment into the distilled
water which is hypotonic compared to the content of ointment. Thus, as the time
increased, more and more of the acetylsalicylic acid was found in the distilled
water. This shows how the drugs are being absorbed from a topical drug delivery
system, where the ointment acts as a carrier for drugs to be absorbed
effectively from the skin into the systemic circulation in body. If the
experiment was allowed to be conducted for a longer period, the UV absorption
value will gradual reach a maximum as the content of the ointment become
isotonic with the surrounding distilled water, this is because equilibrium have
been achieved. No change in the drugs release rate occurs after the equilibrium
point.
However,
this does not occur in the real life situation as the drugs released from the
ointment are not accumulated and always get carried away by the blood
circulation. Thus, concentration gradual is always being maintained for the
absorption of drugs.
In
order to obtain a more accurate result, some precaution has to be noted. We
must follow the proper procedure for the acetylsalicylic acid ointment
production to ensure that the active ingredients are distributed evenly in the
ointment base. When the dialysis bag was put into the beaker containing
distilled water, the outer surface was cleaned and ensured with no residual of
the ointment. The distilled water should be stirred evenly before taking the
sample to ensure that the concentration of drug released form the dialysis bag
is the same throughout the beaker.
3.
Plot a graph of UV absorption against time for the ointments with
different composition of formulation. Compare and discuss the results.
Time (min)
|
Emulsifying Ointment
|
||||
I
|
II
|
III
|
IV
|
||
Average of
UV Absorbance at 300 nm
( x ± SD )
|
0
|
0 ± 0
|
0 ± 0
|
0.026 ±
0.036769553
|
0.014 ±
0.01979899
|
5
|
0.2605 ±
0.229809704
|
0.1245 ±
0.028991378
|
0.0805 ±
0.047376154
|
0.0435 ±
0.010606602
|
|
10
|
0.274 ±
0.239002092
|
0.177 ±
0.012727922
|
0.0855 ±
0.051618795
|
0.054 ±
0.01979899
|
|
15
|
0.292 ±
0.243244733
|
0.188 ±
0.007071068
|
0.1435 ±
0.003535534
|
0.0755 ±
0.0755
|
|
20
|
0.324 ±
0.278600072
|
0.2225 ±
0.004949747
|
0.154 ±
0.005656854
|
0.111 ±
0.041012193
|
|
25
|
0.366 ±
0.301227489
|
0.2915 ±
0.019091883
|
0.1685 ±
0.020506097
|
0.142 ±
0.046669048
|
|
30
|
0.382 ±
0.29274221
|
0.3195 ±
0.00212132
|
0.21 ±
0.01414214
|
0.162 ±
0.05798276
|
|
35
|
0.387 ±
0.288499567
|
0.2875 ±
0.071417785
|
0.228 ±
0.011313708
|
0.162 ±
0.029698485
|
|
40
|
0.414 ±
0.313955411
|
0.315 ±
0.052325902
|
0.2635 ±
0.014849242
|
0.191 ±
0.01979899
|
|
45
|
0.431 ±
0.30688434
|
0.3265 ±
0.03747666
|
0.285 ±
0.01131371
|
0.197 ±
0.02404163
|
|
50
|
0.455 ±
0.455
|
0.3845 ±
0.03181981
|
0.315 ±
0.03676955
|
0.22 ±
0.00707107
|
|
55
|
0.5005 ±
0.5005
|
0.3975 ±
0.0205061
|
0.3395 ±
0.02899138
|
0.226 ±
0.02828427
|
|
60
|
0.517 ±
0.517
|
0.4315 ±
0.00494975
|
0.402 ±
0.0212132
|
0.24 ±
0.01414214
|
|
From
the graph above, it was observed that, the average UV absorbance of the
salicylic acid drug at 300 nm is the highest for emulsifying ointment I. The
next highest average UV absorbance of the salicylic acid is for emulsifying ointment
II, followed by emulsifying ointment III. Whereas emulsifying ointment IV has
the lowest average UV absorbance. For all the emulsifying ointment, the average
UV absorbance increases gradually with time. The results seen in figure 1
indicated that emulsifying ointment I showed maximum average UV absorbance of
drug which is about 0.52 in 60 minutes. It was observed that the average UV
absorbance for emulsifying ointment II and emulsifying ointment III was found
to be around 0.42 and 0.40 in 60 minutes, respectively. Whereas the average UV
absorbance was found to be as low as about 0.24 in 60 minutes in emulsifying
ointment IV.
The
average UV absorbance of the drug indicates the penetration of drug from
dialysis tube into water bath. The high average UV absorbance indicates high
penetration rate of the drug from the dialysis tube and vice versa. The
dialysis tube membrane is expressed as human skin. The possible reason for the
variation in the penetration rate of the drug through the dialysis tube may be
the amount of emulsifying wax and liquid paraffin (oil phase). From the result,
it was found that ointment with highest amount of emulsifying wax and lowest
amount of the liquid paraffin showed the maximum drug penetration. Khalil, Y.
I. et al., 2011 reported that
emulsifying agent concentration had the most profound effect on the drug
release from the ointment base. Emulsifying wax enhance the viscosity of the
ointment and stickiness of the ointment as well. This will prolonged the
contact of the ointments with the dialysis tube membrane which lead to
formation of occlusive layer. The occlusive layer increases the hydration state
of the tube thus enhance penetration of the acetylsalicylic drug. The hydration
state of the membrane is one of the factors affecting drug penetration.
Another
factor that affects the penetration rate of the drug is the solubility of the
drug in the ointment base. Drug release from ointment base requires solubility
of the drug within the formulation. This will allow diffusion of the drug
through the ointment base until it reaches the tube membrane. Emulsifying wax
has the ability to lower the interfacial tension between oily and aqueous layer
in the dispersion medium. This will increase the hydrophilicity of the
ointments which in turn increasing the penetration of the drug into the
ointment structure. As a result, the amount of drug release from the ointment
base is increased as well as the penetration rate of the drug through the
dialysis tube. Besides that, the emulsifying wax provides greater drug
stability in a formulation containing liquid paraffin. This will prevent the
susceptibility of drug to hydrolysis, hence the same amount of drug that
penetrates from the tube would be present in the water bath and shows high UV
absorbance.
Khalil,
Y. I. et al., 2011 also proved that
increasing amount of liquid paraffin led to a retardation of drug release from
formulation. This is because increasing liquid paraffin may decrease the
thermodynamic activity of the drug which can be expressed in term of relative
solubility of the drug. This leads to the retardation of drug release from the
ointment base.
4. What is the function of each
ingredient that are used in the preparation of ointment? How the use of
different content of emulsifying wax and liquid paraffin affect the physical
characteristics of ointment and the rate of release of drug from the ointment.
Function of emulsifying wax is to emulsify and stiffen
the ointments. It helps to keep the oil and water from separating by creating
an emulsion between the oil and water. It also acts as a surfactant that
reduces the surface tension and hence increases acetylsalicylic acid released
from the formulation. A high concentration of emulsifying wax results in a hard
ointment. Big and coarse crystals can be formed by a high percentage of emulsifying
wax and a low content of liquid paraffin. Emulsifying wax retards the drug
release from the formulation. High concentration of emulsifying wax has a
slower drug release compared with the low concentration of emulsifying wax
White soft paraffin is employed as
a base for ointment to enhance the absorption of acetylsalicylic acid through
the membrane into the circulation due to its greasy properties. It also retains
the moisture of the skin by providing a thin layer of oil on the skin surface
to prevent water to evaporate from the skin surface.
Liquid paraffin is used to reduce the viscosity of the base.
It also increases the spreading ability of the acetylsalicylic acid and decreases
the hardness of the ointment. A high proportion of liquid paraffin used in the
formulation produces a watery, greasy and soft ointment which subsequently decreases
the rate of drug released from the ointments.
The acetylsalicylic acid used in the formulation acts as
active ingredient. It often used as an analgesic and antipyretic agent and as
anti- inflammatory drug. In ointment preparation, is used as a topical aid in
the removal of excessive keratin in hyperkeratotic skin disorders. It works as
an exfoliant, promoting the sloughing away of dead skin cells.
CONCLUSION
The
drugs diffuse slowly form the ointment, across the dialysis bag into the
distilled water by diffusion. The composition of ointment will affect its
physical property and the drug’s release rate from the ointment. The drug
released from the ointment, which is correspond to the value of UV absorption
increases with time. Physical characteristics of ointment and the rate of
release of the drug from the ointment will be affected by different composition
of ointment. The more firmer the ointment base the slower release of drug from
ointment. Too much hard paraffin, will make the ointment harder and too much
soft paraffin will make the ointment softer.
REFERANCE
1. Pharmaceutics: the science of dosage form design, Aulton, M.E.2002
2. http://www.teachsoap.com/emulsifywax.html
3.
http://www.esoapsupplies.com/emulsifying_wax.htm
4.
www.buzzle.com/articles/liquid-paraffin-oil.html
5.
www.chemicalland21.com/lifescience/phar/ACETYLSALICYLIC%20ACID.htm
6.
www.pharmpedia.com/Emulsifying_agent
