Experiment 4 - Ointment

Experiment 4: The effects of differences characteristic of active ingredient in formulation of  ointment.

Objectives:
1) To study the effects of difference amount of emulsifying wax, white soft paraffin and liquid paraffin used in the formulation of ointment.
2) To describe and elaborate the texture, clarity and colour of ointment that was formed

INTRODUCTION

Ointment formulation is a semi-solid dosage forms that is suitable for application on the skin and for external use only. An ointment is an oily base preparation and consists of one or more drugs distributed homogenously in base and can be absorbed through the skin for systemic action. A good ointment must have an interesting texture, easy to spread on the skin and release the active ingredient. Ointments are formulated using hydrophobic, hydrophilic, or water-emulsifying bases to provide preparations that are immiscible, miscible, or emulsifiable with skin secretion. Ointment bases are intended to soften but not melt when applied to the skin.

The purpose of an ointment bases include as a vehicle from which the drug may be absorbed by the skin and as a protective layer or emollient for the skin. Different composition of base will greatly affect the pharmacologic effect of a particular drug. This includes stability, penetrability, solvent property, approximately neutral with regard to pH, and ease of application and removal. Therefore in pharmaceutical aspects, choice of bases should be made carefully to obtain optimum drug distribution.

The purpose of the laboratory is studying the effects of different ointment composition on physical characteristics, ointment formed and the rate of drug release from it.

Apparatus:  Weighing balance, 1 weighing boat, 100mL beaker, heater, I set of slap and spatula, 1 set of mortar and pestle, 1 dialysis bag (10cm), thread, glass rod, water-bath, pipette and pipette bulb, Spectrophotometer UV.

Materials:  Emulsifying wax, White soft paraffin, Liquid paraffin, Acetylsalicylic acid, distilled water.

PROCEDURE

1.  50g of emulsifying ointment was prepared through formulation as following:

Emulsifying ointment	Group	Ingredients			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 was taken from the total of 50g and was placed into weighing boat and labelled. The texture, clarity and colour of ointment was observed and compared.

3.  1.5g of Acetylsalicyclic acid was incorporated into 30g of made ointment by using levigation. (Acetylsalicyclic acid powder was crushed into finer particles using mortar and pestle if required.)

4.  The Acetylsalicyclic acid ointment was filled into dialysis bag. Both ends of the bag were tied.

5.  The dialysis bag was placed into 100ml beaker which contains 50ml of saline water and  heated in water-bath to 370C.

6.  One aliquot sample (3-4ml) was pipetted at an interval of 5 minutes. Rate of release of Acetylsalicyclic acid from the ointment tube was determined by using UV-visible spectrometer. The saline water was stirred by glass rod before the sample was taken.

RESULT AND DISCUSSION

1. Compare and discuss the physical properties of ointment prepared. 

Throughout the experiment, we prepare four 50g Emulsifying Ointments of different composition ratio. Emulsifying Ointment I consists of 21g of Emulsifying Wax, 25g of White Soft Paraffin and 4g of Liquid Paraffin; Emulsifying Ointment II consists of 17g of Emulsifying Wax, 25g of White Soft Paraffin and 8g of Liquid Paraffin; Emulsifying Ointment III consists of 13g of Emulsifying Wax, 25g of White Soft Paraffin and 12g of Liquid Paraffin; Emulsifying Ointment IV consists of 9g of Emulsifying Wax, 25g of White Soft Paraffin and 16g of Liquid Paraffin.

Each of the ointments prepared has different physical appearance. In terms of spreadability, Emulsifying Ointment IV is the most spreadable, followed by Emulsifying Ointment III, and Emulsifying Ointment II. As compared, Emulsifying Ointment I is the least spreadable among all.

In the aspect of greasiness, Emulsifying Ointment IV is the greasiest, followed by Emulsifying Ointment III, and Emulsifying Ointment II. Emulsifying Ointment I is the least greasy.

In terms of hardness, Emulsifying Ointment I is the hardest, followed by Emulsifying Ointment II, and Emulsifying Ointment III. Emulsifying Ointment IV is the softest.

Based on these comparisons, we found that the physical properties of Emulsifying Wax are tends to be more solidified in semisolid preparation. We can know this through the observation on its hardness, greasiness and spreadability. It tends to decrease in greasiness and spreadability while increasing in hardness.

On the other hand, Paraffin Oil tends to be more liquidified in semisolid preparation. Based on its physical properties, Paraffin Oil is increase its greasiness and spreadability while decreasing in hardness.

Therefore, to prepare an ideal ointment, we must balance the composition of Emulsifying Wax and Paraffin Oil so that the ointment produced will not be neither too hard nor too soft. 

2. Plot a graph of UV absorbtion against time. Explain

This graph shows the reading obtained from the UV spectrometer. The UV spectrometer measures the releasing of acetylsalicylic acid from the ointment in the dialysis bag immersed in the 100 ml 37°C distilled water. The mass of emulsifying wax is 9 g, white soft paraffin is 25 g, and liquid paraffin is 16 g. Overall, the graph shows the gradual increasing in the absorption of UV with a large increase at the initial. Initially, at the first 10 minutes, the UV absorption value surge up follow by gradual increasing of the UV absorption value until 30 minutes.                                 

            The great increase in the UV absorption value at the first 10 minutes is due to the great concentration difference between content in dialysis tube and the distilled water. The content of in the dialysis bag is hypertonic to the distilled water. So, large amount of ointment with acetylsalicylic acid diffuses to the distilled water with high concentration gradient different. The amount of ointment diffuse is proportional to the acetylsalicylic acid. The high value of UV absorption may due to the presence of residual at both end of the dialysis bag, left during the insertion of ointment into the dialysis bag. So when the dialysis bag is immersed in the distilled water, the residual will dissolve in the water. This makes there are content of acetylsalicylic acid that are not from the diffusion through the dialysis bag. After the residual at both end of dialysis bag has dissolved all, the acetylsalicylic acid diffused out only through the pore of dialysis bag, so the readings between 10 to 20 minutes show regular increase. A sudden large increase in the UV absorption does not occur after 10 minutes as the concentration gradient across the dialysis bag decrease, the amount of acetylsalicylic acid in the distilled water increases with time. The gradual increase in the UV absorption indicates the gradual release of acetylsalicylic acid from the dialysis bag. The concentration of content in distilled water gradually equals the concentration of the content in dialysis bag. This will result in the reduced increase in the UV absorption when time passes by.

            If the experiment is continued beyond 30 minutes, 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. The content in dialysis bag is isotonic to the distilled water content concentration.

            Some of the precautious steps can be taken during conducting the experiment are to avoid over stirring the distilled water as this might break the dialysis bag and result a large amount release of the ointment from it. Besides, the residual that retained at both end of the dialysis bag should be removed before immersing the dialysis bag in the distilled water to ensure accuracy of the result. The rope should tie both end of the dialysis bag tightly to prevent leakage of the ointment. The cuvette should be cleaned for the fingerprint around the surface of it so that the measurement is correct. The distilled water in the beaker should cover the whole dialysis bag to ensure consistent diffusion.

3. Plot a graph of UV Absorption against time for ointment formulations of different composition. Compare and discuss the results obtained.

Time (min)	UV Adsorption
	0	5	10	15	20	25	30
UV absorption at 300nm	0.063	0.121	0.212	0.224	0.235	0.294	0.331

The ideal ratio of amount Emulsifying Wax, White Soft Paraffin and Liquid Paraffin in the preparation ointment is 30 : 50 : 20. Theoretically, an ointment that contains the highest amount of emulsifying wax and lowest amount of liquid paraffin will take longer time for the acetylsalicylic acid to penetrate from the dialysis membrane. This results in the lowest reading of UV absorption by the acetylsalicylic acid. This can be explained by the theory stated that when there is a low amount of emulsifying wax,  the acetylsalicylic acid cannot disperse well in the ointment. As we increase the amount liquid paraffin in the formulation, greater amount of acetylsalicylic acid is able to penetrate the dialysis membrane at a faster rate. This is due to the role of liquid paraffin in the formulation that improves hydration, thus increase the effectiveness of the absorption of the ointment at the percutaneous membrane.

In the experiment conducted, four formulations were prepared. The formulations possessed different amount of emulsifying wax and liquid paraffin. Results obtained have shown that Formulation 1 which contained the least amount of liquid paraffin resulted in the lowest UV absorption value. Formulation 3 showed higher UV absorption than Formulation 1. This is followed by Formulation 4 and Formulation 2 with the greatest amount of UV absorption. As the amount of emulsifying wax reduces, with an increase in the amount of liquid paraffin, the UV absorption of acetylsalicylic acid should increase. From the results obtained, there is a slight inaccuracy because supposedly Formulation 2 shows lower UV absorption than Formulation 3 and Formulation 4. This inaccuracy might be due to several possible errors done during the experiment.

The possible errors may be due to the inaccurate measurement of amount of ingredients used in the formulation prepared. This will affect the permeation rate of Acetylsalicylic acid and the UV absorption. Secondly, the absorption of UV may get affected by the inaccurate or different amount of ointment filled in the dialysis bag. Besides, the presence of contaminants on the dialysis bag could also contribute to the inconsistent results. Moreover, the spillage of the drug from the dialysis could be one of the errors that could alter the results. 

4. What is the function of each materials used in this ointment preparation? How the different ratio of emulsifying wax and liquid paraffin used influence the physical characteristics of an ointment formulation and the rate of drug release from the ointment preparation.

Liquid paraffin is used as a blending base and as an emollient. It also helps to increase the spreadibility of the ointment to be easier to be applied on the skin. Besides, it is usually formulated with white or yellow soft paraffin to achieve the required viscosity for application to the required site.

White soft paraffin has also give advantage as a skin protectant. It is a hydrophobic compound that repels water and retaining the moisture of the skin. Since white soft paraffin is a rich emollient, it has the ability to penetrate deeper into the skin than other lotions or compounds. Its contribution to the thickness of the compound forms a barrier on the skin that further prevents additional water from escaping the top layers of the skin.

Emulsifying wax has emulsifying properties. It has the function of increasing the viscosity of oil-in-water emulsions, thereby improving their stability, and also gives emollient effect when added to paraffin ointment. High ratio of emulsifying wax in the ointment will increase the rate of release of drug as it act as surfactant that decrease the surface tension and hence increase absorption. It will assist in improving the consistency and texture of final product without leaving a greasy film on the outer skin after application. It also controls the rheological properties of the system by their interaction with water and other excipients in the external phase. The unique characteristics of emulsifying wax give certain solidity to emulsified solutions, enables product to easily spread and glide on the skin. It is also used as an emulsifier, which enables the blend of oil and water to prevent bleeding and phase separation.

Liquid paraffin is a viscosity builder. Thus, the higher the amount of liquid paraffin used, the more viscous of an ointment and the slower the drugs or active ingredients being released. High contain of liquid paraffin will cause the ointment become greasy. Liquid paraffin is usually used in combination with white soft paraffin. An appropriate combination of liquid paraffin with white soft paraffin will give an ointment with desirable properties. Emulsifying wax is a penetration enhancer. Thus, the higher the amount of emulsifying wax added, the faster the drug release rates. Besides, an emulsifying wax is to soften and give thickness to ointments. Hence, a high content of emulsifying wax cause the ointment become hard. In conclusion, the standard ratio of emulsifying wax: white soft paraffin: liquid paraffin is 3:5:2. The ratio of emulsifying wax must be higher than liquid paraffin as emulsifying wax acts to release drug rapidly from the ointment preparation. Liquid paraffin is used to increase the spredibility of the ointment.

CONCLUSION

Different compositions of bases for ointment formulation affect the physical characteristics and its release rate of drug.

REFERENCES

1.http://intranet.tdmu.edu.ua/data/kafedra/internal/pharma_3/lectures_stud/Industrial%20drugs%20technology/4-course/English/Ointmants..htm

2.    Aulton, M.E.2002. Pharmaceutics: The Science of Dosage Form Design. Edinburgh: Churchill Livingstone.  

3.      Pharmaceutics, The Science of Dosage Form Design, Michael Aulton, 3rd Edition 

4.      Kalur, G. C, Frounfelker, B. D, Cipriano, B. H, Norman, A.L, Raghavan, S. R, 

5.      ViscosityIncrease with Temperature in Cationic Surfactant Solutions Due to the

6.      Growth of Wormlike Micelles, 2005, American Chemical Society.