Title:
Effects of different ingredients on the characteristics
of ointment formulation.
Objectives:
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.
Introduction:
Ointments
or sometimes known as an emollient or moisturizer are semisolid preparations
intended for external application that usually contain medicinal substances. An
ointment is a homogeneous,
viscous, semi-solid preparation, most commonly greasy, thick oil (oil 80% -
water 20%) with a high viscosity that is intended for external application to
the skin or mucous membranes.
It
is used to relieve the symptoms of dry skin conditions, such as cracked, scaly
and itchy skin. The emulsifying ointment leaves a thin layer of oil on the
skin's surface that stops water evaporating. This results in a soothing,
softening and moisturising effect. In general this drug is used to moisturise
and soften dry skin. They are used as emollients or for the application of
active ingredients to the skin for protective, therapeutic, or prophylactic
purposes and where a degree of occlusion is desired.
The
desirable qualities in ointment included smooth, never gritty. The choice of an
ointment base is of the utmost importance, and although it may be impossible
for any single base to be ideal in every respect, the following are standards
for which we strive:
- The base in no way adversely affects a wound to which it is applied.
- It is pharmaceutically elegant.
- It does not cause sensitization or irritation, either to unabraded or traumatized skin.
- It is prepared with relatively little difficulty.
- It is neutral (neither acidic nor basic)
- It does not dehydrate the area to which it is applied.
- It is non-greasy and non-staining.
- It has permanency, good keeping qualities, and neither becoming rancid nor supporting microbial growth.
- It is compatible with a wide range of medicinal substances and with other bases with which it is likely to be mixed.
- It releases the incorporated medication effectively to the site of application, and if so intended, passes into or through the skin.
- It is washable. Unfortunately, not all ointments, creams and pastes meet this requirement.
More
trituration is necessary in preparing powders for incorporation into ointments
than powders to be used in tablets or capsules. Methods of preparation of
ointments included trituration and fusion. In trituration, finely subdivided
insoluble medicaments are evenly distributed by grinding with a small amount of
the base followed by dilution with gradually increasing amounts of the base,
while in fusion, the ingredients are melted together in descending order of
their melting points and stirred to ensure homogeneity.
This experiment is to find out the
effect of different formulation of ointment on the physical characteristics and
the drug release rate.
Apparatus:
Weighing
instrument, weighing boat, 100ml beaker, heater,1 set of cream and spatula,
mortar and pestle, dialysis bag (10cm), thread, glass rod, water-bath, 1 set of
pipette (5 ml) and pipette-bulb,1 plastic cuvette and spectrophotometer UV/Vis.
Materials:
Emulsifying
wax, white soft paraffin, liquid paraffin, acetylsalicylic acid, distilled
water
Methods:
1. 50g of Emulsifying Wax was prepared
based on the following formulation:
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 30 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
(100ml) filled with distilled water (50ml) 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 UV-visible spectrometer
. The distilled water is made sure to be stirred with the glass rod before the
sample was taken.
Results:
Figure 1: Texture, clarity and the
color of the ointment
Table
1: UV absorption of ointment
Discussion:
1.
Compare
the physical properties of ointment. Give reason.
Ointments
are composed mostly of fluid hydrocarbons meshed in a matrix of higher melting
solid hydrocarbons.
Ointment I is the least greasy and the hardest to spread
whereas ointment IV is the most greasy and easiest to spread. This is because
from ointment I to IV, the amount of liquid paraffin increases and the amount
of emulsifying wax decreases. Liquid paraffin is a hydrocarbon base. It is
immiscible with water thus it is low water absorbing and has the characteristic
of greasiness.
The
amount of liquid paraffin increases from I to IV, but the amount of emulsifying
wax is decreasing. The clarity for all four ointments is poor due to presence
of white soft parafin and emulsifying wax. Ointment 4 gives yellowish colour as it is made up of a
small amount of emulsifying wax and large amount of liquid paraffin compared to
the others three ointment which show white colour
The
presence of the liquid paraffin will make the ointment smoother. If lesser
amount of emulsifying wax is used, then the “interlocking structure” will not
be formed completely. Emulsifying wax gives the texture and characteristics
that resembles sand to the ointment. So, the ointment formed is less hard.
2.
UV
absorption graph is plotted against time. Give explanation.
The
graph above shows the relationship between the UV absorption against time for
acetylsalicylic acid ointment. Based on the graph, it shows the absorption of
UV is gradually increased as the time increase. This means that the longer the
time, the higher the amount of drugs passing through the membrane or the higher
the bioavailability. Theoretically, the acceleration of UV absorption at the
first 5 minutes is caused by the content in dialysis bag is more hypertonic compared
to the surrounding distilled water.
As the experiment proceeds, the content in the dialysis bag becomes
more isotonic to the distilled water because some particles of acetylsalicylic
acid already pass through the dialysis bag to the distilled water. This will
result in the reduced gradient of the graph when time passes by. If the
experiment is continued, it may result in a straight line graph as the
concentration of acetylsalicylic acid in the distilled water equals to the concentration
of acetylsalicylic acid at the dialysis bag.
From the graph above, we can observe a few points where the UV
absorption is slightly decrease that may be caused by some error during
experiment such as we did not stir the solution before pipetting, we did not clean
the clevette plastic properly before test for UV spectrometry and so on.
3.
Discuss the effect of different formulation of ointment on drug
release rate
Theoretically
the descending order of concentration of acetylsalicylic acid diffuse into the
distilled water should be formulation IV, III, II and I.
Emulsifying wax is water miscible base, while liquid paraffin is hydrocarbon
base. Emulsifying wax helps in dispersing the hydrophilic acetylsalicylic acid,
while liquid paraffin assists in diffusion of acetylsalicylic acid out of the
ointment, through the dialysis bag into the distilled water. With a high
proportion of emulsifying wax and low proportion of liquid paraffin,
formulation I is the hardest among the four formulations and should has the
slowest release rate. Acetylsalicylic acid is hydrophilic, therefore it
disperses well in the ointment with high percentage emulsifying wax. However,
the oil phase (liquid paraffin and soft paraffin) is not enough for the acetylsalicylic
acid to diffuse through the membrane. Hence amount of acetylsalicylic acid in
the distilled water should be low.
The error in the experiment might occur due to improper filling of ointment
into the dialysis bag, causing presence of ointment on the surface of the bag.
Another possibility is that there is small leakage at the dialysis bag, which
causes the acetylsalicylic acid to diffuse through the dialysis bag into the
distilled water at a higher rate with higher concentration. The error may also
due to the threads tying the both ends of the bag are loosen.
Precaution step of obtaining an accurate result should be carried out. The
surface of dialysis bag should be cleaned before immersing it into the
distilled water. Ointment should be filled into the bag gently and carefully to
prevent the leakage of the bag. Distilled water should be stirred before
obtaining the sample, so that the acetylsalicylic acid diffuse out from the
ointment dispersed evenly in the distilled water.
4. What is
the function of each materials used in preparation of the ointment? How can
different the composition of Emulsifying wax and Liquid Paraffin can influence
the physical properties of the ointment and the rate of diffusion of the drug
from the ointment?
The components contain in an
ointment are emulsifying wax, white soft
paraffin, liquid paraffin, acetylsalicylic acid and distilled water.
Firstly, emulsifying wax is an anionic emulsifying agent and will acts as a
mixer to blend two phases of oil-soluble and water-soluble and this phase will
formed a layer known as interface. The wax is dispersed in the oil phase and
aqueous phase is added at the same temperature. The ingredients of emulsifying
wax are Cetearyl Alcohol, Polysorbate 60, PEG-150 Stearate, and Steareth-20. It
has the characteristics of cetyl alcohol combined with the viscosity building
effect of stearyl alcohol as an effective thickener and helps form stable
emulsions.
Meanwhile, white soft paraffin and liquid paraffin are both acts as
hydrocarbon bases. The characteristics of hydrocarbon bases are it is a stable,
bland and chemically inert and will mix with other substances in the
formulation of ointment. White soft
paraffin is also known as white petroleum jelly. This is not an active
ingredient as such, but works as a moisturizer by providing a layer of oil on
the surface of the skin to prevent water evaporating from the skin surface and
it is a very greasy moisturizer and acts as stabilizers. Meanwhile, liquid paraffin is a highly refined
white mineral oil that is white, odourless, tasteless and waxy substance. This
will help in giving the opacity of the ointment. If the amount of liquid
paraffin in the ointment is high, the higher shining effect of the ointment.
Same as white soft paraffin, it also helps in emollient properties. White soft
paraffin and liquid paraffin are combined together to achieve viscosity for
application for the required site.
Acetylsalicylic
acid
acts as an active ingredient in the ointment ingredient. Acetylsalicylic acid
also known as aspirin will have effect of antipyretic, anti-inflammatory and
analgesic by inhibit the same enzyme cyclooxygenase, aspirin (but not the other
salicylates) does so in an irreversible manner and, unlike others, affect more
the COX-1 variant than the COX-2 variant of the enzyme. Distilled water function is to mix all ingredients together and
give moisture effect.
The release of a drug from a
semi-solid system is dependent on the type of base into which the drug is
incorporated as well as the solubility of the drug. From the experiment,
primarily oleaginous bases release substances slowly and unpredictably, since
water cannot penetrate them sufficiently to dissolve the drug and allow for
diffusion. Water miscible or primarily aqueous bases tend to release drugs more
rapidly, especially drugs which are lipophilic and have a poor affinity for the
hydrophilic base. In the experiment, ointment I has higher release of
acetylsalicylic acid because of higher amount of emulsifying wax and lower
amount of liquid paraffin while ointment IV has lesser release of
acetylsalicylic acid because it has higher amount of liquid paraffin and lesser
amount of emulsifying wax.
Conclusion:
The ointment composition will affect the physical property
and the drug release rate from the ointment. The higher the amount of
emulsifying wax, the ointment will be harder. The balance
between the amount of emulsifying wax and liquid paraffin in the ointment is
important in achieving the desirable traits without comprimising the rate of
drug release in order to demonstrate the ideal release of drug in systemic
circulation.
References:
1. A. J.
Winfield, R. M. E. Richards. 2004. Pharmaceutical Practice. 3rd Edition. China
2.
Reynolds, J.E.F. 1993. Martindale:
The Extra Pharmacopoeia. 30th
Edition. London
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