OINTMENT

TITLE:

Effects of different ingredients on the characteristics of ointment formulation

OBJECTIVE:

1.      To investigate the effects of different composition of ointments to the physical characteristics of the ointments formed and the rate of drug released from the ointments.

INTRODUCTION:

            Ointment formulation is a type of semisolid dosage preparation. Ointment is also known as an emollient and usually contains medicinal substances. Ointment can be used for external application, such as applications on the skin and mucous membranes. Ointment also has viscous properties and is made up of 80% of oil and 20% of water. A good ointment formulation needs a smooth texture, so that the ointment can be easily apply to the skin and also allow the release of the active ingredients at the correct rate. The ointment formulation contains one or more active ingredients, that comes in either liquid or powder form that is dissolved or dispersed homogenously in an oily semisolid carrier. An ideal ointment base must have several properties. The ointment base must be pharmaceutically elegant and does not cause any sensitization or irritation to the affected skin. The base must be neutral, non-greasy and non-staining. The base must also compatible with a wide range of medicinal substances, able to mix with other bases and also does not support any microbial growth.

In pharmaceutical practice, ointment preparation is used to treat and relieve symptoms of dry skin conditions and also exert an emollient effect on cracked and itchy skin. The ointment will also give a soothing, softening and moisturizing effect by leaving a thin layer of oil on the surface of the skin. Ointments are also used to reduce further water loss from the skin.

APPARATUS:

Weighing balance, 1 weighing boat, 100mL beaker, heater, 1 set of glass slab and spatula, 1 set of mortar and pestle, 1 dialysis bag 10cm, 2 threads, 1 glass rod, water bath, 1 set of 5mL pipette and pipette bulb, 1 plastic cuvette and UV visible spectrophotometer.

MATERIALS:

Emulsifying wax, white soft paraffin, liquid paraffin, acetylsalicylic acid, distilled water.

PROCEDURE:

1.      A 50g emulsifying ointment was prepared using the following formula as shown below:

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.      5g of the ointment formed was taken and placed into the weighing boat and the ointment was labelled. The texture, clarity and the colour of the ointment formed was then described and compared. 

3.      1.5g of acetylsalicylic acid powder was incorporated into 30g of ointment that was prepared using levigation technique.

4.      The acetylsalicylic acid ointment was filled into the dialysis bag and the both ends of the bag were made sure that they were tied neatly, as shown in the diagram below:

 

5.      The bag was placed into the 100mL beaker that was filled with 50mL distilled water, which was already heated up to the temperature of 37°C.

 

6.      At every interval of 5 minutes, one aliquot sample of 3-4 mL was pipetted and the release of acetylsalicylic acid from the ointment base was determined using the UV visible spectrometer. The distilled water was then made sure that the distilled water was stirred with the glass rod before the sample was taken.

Time (min)	UV absorption
	0	5	10	15	20	25	30	35	40	45	50	55	60
UV absorption at 300 nm	0.052	0.059	0.135	0.169	0.191	0.206	0.218	-	-	-	-	-	-

RESULTS:

Differences of physical appearance of ointments with different compositions

Group	Material (g)				Texture of ointment			Clarity	Colour
	Emulsifying wax	White soft paraffin	Liquid paraffin	Spreadibility		Greasiness	Hardness
1 & 5	21	25	4	Most difficult		Least greasy	Hardest	Turbid	White
2 & 6	17	25	8	Difficult		Relatively greasy	Hard	Turbid	White
3 & 7	13	25	12	Intermediate		Greasy	Soft	Turbid	White
4 & 8	9	25	16	Easy		Most greasy	Softest	Turbid	White

UV absorption against Time

Time (min)	UV absorption
	0	5	10	15	20	25	30	35	40	45	50	55	60
UV absorption at 310mm	0.052	0.059	0.135	0.169	0.191	0.206	0.218	-	-	-	-	-	-

DISCUSSIONS:

1.      Compare the physical appearance of the ointments formed and give your comments.

In this experiment, the ointment from group 1 and 5 contain 21 g of emulsifying wax and 4 g of liquid paraffin while ointment of Group 2 and 6 contain 17 g emulsifying wax and 8 g of liquid paraffin. Meanwhile, ointment of Group 3 and 7 contain 13 g of emulsifying wax and 12 g of liquid paraffin whereas ointment from Group 4 and 8 contained 9 g of emulsifying wax and 16 g of liquid paraffin. All the four groups use the same amount of white soft paraffin which is 25 g. The amount of emulsifying wax will determine the hardness of the ointment while the amount of liquid paraffin will contribute to the texture of the ointment whether it has oily and smooth texture.

Based on the results obtained, group 1and 5 produces an ointment that is hardest, least greasy and most difficult to spread among all groups. This is because the amount of emulsifying wax used is highest among all. This will then cause the hydrophilic drug to be dispersed into the ointment by the emulsifying effect. The hardness of the ointment causes the drug to be difficult to diffuse out into the water. Group 4 and 8 uses small amount of emulsifying wax produces an ointment that is softest, most greasy and easily spread among all. As the hardness is low, it will not give many effects on the diffusion of the drug. Ointments which been produced by group2, 6 shows the texture of ointment which is difficult to spread, relatively greasy and hard. The texture of the ointment produced from group 3 and 7 are relatively the same with slight difference  from the ointment produced by group 2 and 6 as they shows intermediate spreadiblity, greasy and soft texture.

In term of spreadibility, ointment from group 4 and 8 are most easy to spread followed by group 3 an7, group 2 and 6 and group1 and 5 which is poorly spread. In term of greasiness, group 4 and 8 that used higher amount of liquid paraffin result in a greasy ointment. For grittiness, group 1and 5 that uses ingredients with higher amount of emulsifying wax tend to obtain a gritty ointment.  All of the eight groups show white color of ointment, but there is a slight difference in the color intensity. Group 4 and 8 shows light color of ointment with less intensity of white color as this ointment contains high amount of liquid paraffin. The intensity of white color increases with decreasing amount of liquid paraffin used where group 1 and 5 shows high intensity of white color ointment. In term of clarity and transparency, all groups produce turbid ointments.

2. Plot the graph of UV absorption against time. Give explanation.

Graph of UV absorption against Time

Time (min)	UV absorption
	0	5	10	15	20	25	30	35	40	45	50	55	60
UV absorption at 310mm	0.052	0.059	0.135	0.169	0.191	0.206	0.218	-	-	-	-	-	-

In this experiment, the dialysis bag indicates the skin membrane where the absorption of drug is entering the circulation by passing through it. The concentration of drug in the distilled water represents the amount of drug absorbed into the circulation that is the bioavailability of the drug.

UV absorption refers to the amount of drug that passes through the membrane. Based  the graph, we can see that UV absorption at 310mm which carried out at 37 °C is proportional to the time throughout the experiment. Theoretically, UV absorption is proportional to the time of acetylsalicylic acid release from the tube that is exposed to the dialysis environment. The UV absorption of the ointments increases when the time increases, which means that the longer the time, the higher the amount of drugs passing through the membrane or the higher the bioavailability is.

The gradient of the graph refers to the releasing rate of the acetylsalicylic acid from the membrane of the tube. From the graph, we can see that the gradient of the graph increases as the time increases until time 30^th. This is because in the beginning of the experiment, distilled water is much hypotonic to the ointment which consists acetylsalicylic acid tended to diffuse out from the tube to the hypotonic solution (distilled water). As the experiment proceeds, the solution in the dialysis bag becomes isotonic to the distilled water as some of the acetylsalicylic acid has been moved to the distilled water. This shows that the equilibrium for diffusion of acetylsalicylic acid into and out of the tube is achieved. Hence, the gradient of the graph decreases. This indirectly shows that the drug had achieved its bioavailability.

When the releasing rate reduced (gradient of the graph decreased). This condition can be explained as the graph achieved its saturation point. At the late stage of experiment, the releasing rate increased sharply.

Some errors have been made and resulted in the fluctuation of the graph. Firstly, this may due to tube are not tied tightly enough and lead to the leakage on the membrane therefore affect the result obtained. Secondly, errors occur when insufficient stirring of the distilled water until uniform before sample is taken out for measurements. The concentration of acetylsalicylic acid may not be consistent if the distilled water in the beaker was not stirred uniformly. This may affect the value of UV absorption. Thirdly, error occur when the temperature inside the water bath are not constant. It should be always maintain at uniform temperature 37°C.

Some precautions need to be taken in order to reduce the errors. The dialysis bag has to be tied tightly and immersed completely in the distilled water in order to get an accurate result. In addition, the smooth surface of the cuvette should not face the source of UV light and the smooth surface should be cleaned before it is placed into the device. Moreover when we were holding the cuvette, it was not advisable to hold the smooth surface where there is a triangle symbol on it. Lastly, the technique of using spectrophotometry device also plays a vital role in getting accurate results.

4.      What is the function of each ingredients used in the preparation of the ointment? How does the usage of different compositions of the emulsifying wax and liquid paraffin affects the physical properties of the ointment and the rate of drug release from it?

Emulsifying wax acts as an emulsifying agent which decreases the interfacial surface tension so that the drug particles can be distributed uniformly in the ointment and to prevent any sedimentation from occurring. White soft paraffin acts as moisturizers, as the skin is smoothed and softened, its ability to absorb medicines is increases thus, it improves the ability of medicines to penetrate the skin. Liquid paraffin acts as emollient, liquid paraffin adsorbed on the skin and provides an emollient film that reduces water loss from the outermost layer of the skin to the environment. It also used to reduce viscosity of the base, softens the ointments formed so that it can be spread and applied easily.  Acetyl salicyclic acid acts as active ingredient in the ointment and thus gives the therapeutic effect of the ointment produced. It may help to reduce the redness, inflammation, analgesic effect in topical usage.

The composition of the bases in an ointment formulation affects the overall physical properties of the ointment produced. The higher the concentration of the emulsifying wax, the harder of the ointment produced. In contrast, for liquid paraffin, it reduces the viscosity of ointment, therefore the higher the concentrations of the liquid paraffin, the lower the viscosity of the ointment, contribute to the softer ointment. By increasing the concentration of emulsifying wax and reducing the amount of liquid paraffin, the ointment will become harder and less greasy. Thus, lower portion of emulsifying wax and higher portion of liquid paraffin is preferred in order to increase the spreadability and greasiness and reducing the hardness of the ointments in order for the drugs to be released from the formulation and penetrate the skin. Therefore, the composition of the bases in an ointment contributes in the rate of drug release. 

CONCLUSION:

            Based on the experiment, we can conclude that different amount of emulsifying wax will affect the ointment’s characteristic. It can affect spreadibility, greasiness, and hardness of ointment. The higher the amount of emulsifying wax, the lower the ability of ointment to flow and the texture of ointment become harder. The greater the amount of emulsifying wax, the higher the greasiness of ointment.

REFERENCE:

1.      http://www.netdoctor.co.uk/skin-and-hair/medicines/emulsifying-ointment-bp.html

2.      Aulton, M.E. 2002. Pharmaceutics: The science of dosage form design. Edinburgh: Churchill Livingstone.

3.      2. Florence,A.T. & Attwood, D. 1998. Physico-chemical principles of pharmacy. 3rd Ed. New York: Macmillan.