EXPERIMENT 1 : OINTMENT

EXPERIMENT 1: OINTMENT

Title : An assessment of the effects of different content on the characteristics of an ointment formulations

Objective

To study the effects of different ointment composition on the physical properties formed and the rate of drug released from it.

Date of Experiment : 1 April 2015

Introduction

Ointment formulation is a semisolid dosage form that is suitable for external application on skin. It is an oily preparation that contain one or more active ingredients that is soluble or spread homogenously. A good ointment must have an appealing texture, easy to use on skin characteristic as well as releasing it active ingredient from it.

Generally, ointment composed of active ingredient either powder or liquid that is incorporated into the oily semisolid. In Pharmaceutics, ointment preparation is used to act as local treatment at application site, increasing the moisture of the skin (emollient effect).

Procedures

1)     Emulsifying Ointment (50 g) was prepared using the formula below :

Emulsifying Ointment	Group	Ingredients			Total (g)
		Emusifying Wax	White soft paraffin	Liquid paraffin
I	1,5,9	21	25	4	50
II	2,6,10	17	25	8	50
III	3,7,11	13	25	12	50
IV	4,8,12	9	25	16	50

2)     5 g of the emulsifying ointment was weighed using the weighing boat. Explain and compare the texture,purity and the colour of the ointment.

3)     1.5 g of Acetyl salicylic acid was then incorporated into the 30 g of ointment by using the levigation method.(Grind the powder of salicylic acid using the mortar and pestle if needed)

4)     Acetyl salicylic acid was then filled into the dialysis bag and both of the end of the beg were tied tightly, as shown in the figure below:

5)     Dialysis beg then was immersed into the beaker (100ml) contain 50 ml  of distilled water that was heated at 37 degree celcius at room temperature.

6)     For every 5 minutes, pipette (3-4ml) from the dialysis bag and determined the separation of acetylsalicylic acid using the spectrometer UV-Visible. Distilled water was stirred before taking the sample.

Time (min)	UV Absorption
	0	5	10	15	20	25	30	35	40	45	50	55	60
UV absorption at 310 nm

Result:

Time (min)	UV absorption
	0	5	10	15	20	25	30
UV absorption at 310nm	0.36	0.39	0.413	0.415	0.498	0.525	0.544

Discussion

In this experiment, the dialysis bag indicates the skin membrane where drug is absorb through it. The concentration of drug in the distilled water represents the amount of drug absorbed into the circulation which also known as the bioavailability of the drug.

There are several factors that we recognized that may lead to error while doing this experiment which are :

1.       Difficulties in filling the ointment inside the small dialysis bag which may cause the amount inside the dialysis bag not accurate. Therefore, to overcome this problem, the dialysis bag filled with the ointment should reweight before putting inside the beaker containing distilled water.

2.       The dialysis bag also may contaminated while the process of filling the ointment inside the dialysis bag. This may affect the data obtained.

3.       Consistency of the data also may be affected as the data from different composition of ointment are prepared by different group.


Question

1)   Comparison of the physical properties of the ointment of different formulations.

The ointment preparation has similar content of the white soft paraffin but different formulation of the emulsifying wax and liquid paraffin. The preparation of the emulsifying ointment is 50g with combination of the emulsifying wax, white soft paraffin and also liquid paraffin. The lower the emulsifying wax the softer the ointment preparation. The small amount of the liquid paraffin caused the texture less spread upon application. The large amount of the emulsifying wax causes the ointment become hard and less greasy.

Emulsifying ointment	Texture	Properties
I	Lowest spreadibility, hardest	Have smallest amount of liquid paraffin
II	Low spreadibility, less greasy, hard	Have small amount of liquid paraffin
III	Spread, soft and greasy	Have large amount of emulsifying wax and liquid paraffin
IV	Most spread, softer and more greasy	Have large amount of liquid paraffin and small amount emulsifying wax

2)   Graph of UV against time.

Time (min)	UV absorption
	0	5	10	15	20	25	30
UV absorption at 310nm	0.36	0.39	0.413	0.415	0.498	0.525	0.544

In this experiment , the dialysis bag is resembled to the phospholipid bilayer of the cell membrane of human where the absorption occurs across the membrane into the distilled water which is resembled to the blood plasma. The temperature of distilled water is maintained at 37ºC which is the temperature of human body.

The amount of drug absorbed into the blood circulation is represented by the concentrations of the drug in the distilled water. The UV absorption represents the concentration of the drug that crosses the membrane and reaches into  the distilled water.

In theory, the UV absorption is proportional to the time of the release of salicyclic acid across the membrane to distilled water. The gradient of the graph shows the rate of drug release across the membrane of dialysis bag.

The graph shows that as the time increases, the concentration of the salicyclic acid in the distilled water is increasing. Along the time until a particular point, the gradient of the graph decreases thus the releasing rate is reduced. Along the progression of the experiment, the concentration of salicyclic acid in the dialysis bag and the distilled water become isotonic because the salicyclic acid keeps moving into the distilled water. The gradient of graph decreases because the salicyclic acid diffuses into and out of the membrane of dialysis bag in an equilibrium state. At the late stage, the releasing rate increases. This may be contributed by the experimental error such as leakage of the drug whereby the thread is not tight tightly enough or  the distilled water is stirred too vigorously. 

3) Graph UV against time for ointment formulation that contain different composition.

Time (min)		Average of UV absorption at 310nm (x ± SD)
		0	5	10	15	20	25	30
	I	0	0.060	0.124	0.138	0.144	0.203	0.315
	II	0.202	0.205	0.194	0.239	0.888	0.318	0.347
	III	0	0.088	0.076	0.1666	0.153	0.087	0.1627
	IV	0.128	0.137	0.162	0.173	0.255	0.476	0.522

From the graph above, the formulation 1 has the lowest concentration of acetylsalicylic acid in the distilled water. Theoretically, low concentration of acetylsalicylic acid in the distilled water should be shown. Physically, formulation 1 ointment is harder than the other ointments. Formulation 1 shows slow release rate due to the high proportion of the emulsifying wax and low proportion of liquid paraffin. The hydrophilic acetylsalicylic acid can disperse uniformly in the ointment, due to high proportion of the emulsifying agents (emulsifying wax). However, the oil phase (liquid paraffin and soft paraffin) is not enough for the acetylsalicylic acid to diffuse through the membrane. Hence concentration of acetylsalicylic in the distilled water is low.

From the book Differential diagnosis in dermatology written by Richard Ashton, Barbara Leppard, the ideal formulation of ointment has the percentage of emulsifying wax, white soft paraffin and liquid paraffin at 30%, 50%, 20% respectively.

 The graph shown indicates that formulation 3 has higher concentration of acetylsalicylic acid in distilled water than formulation 2. Theoretically, as the amount of emulsifying wax decrease and amount of liquid paraffin increases, the acetylsalicylic acid can diffuse through the membrane better which means that isotonicity can be achieved between ointment and the surrounding distilled water in a faster way. In formulation 2, the percentage of emulsifying wax, white soft paraffin and liquid paraffin are 34%, 50%, 16% respectively. Meanwhile, in formulation 3, the percentage of emulsifying wax, white soft paraffin and liquid paraffin are 26%, 50%, 24% respectively. Both formulations shows only 4% difference with the ideal formulation. Thus, these formulations encourage the diffusion of drugs into the distilled water through the membrane.

Formulation 4 has the highest concentration of acetylsalicylic acid in distilled water. This is because there is a high amount of liquid paraffin to assist in the diffusion of acetylsalicylic acid, and sufficient emulsifying wax causes acetylsalicylic acid able to disperse properly in ointment. Therefore, acetylsalicylic acid has high concentration in distilled water.

 As the time goes on, the concentration of acetylsalicylic acid in distilled water gradually increases for every formulation. However, in formulation 2, 3 and 4 there is a decrease in concentration during 20 minutes to 25 minutes. This is due to uneven stirring or absence of stirring before taking out the volume, the concentration of acetylsalicylic acid is unevenly distributed in the distilled water. Hence, the volume taken out maybe less concentrate than the previous concentration.

4. What is the function of each material in the preparation of the ointment? How the does the different formulation of the emulsifying wax and the liquid paraffin affect the physical properties of the ointment formed and the release rate of the drug from the ointment?

Materials	Functions
Emulsifying wax	Emulsifying agents keep the oil and the water from separating  by creating the an emulsion between oil and water
White soft paraffin	Act as moisturiser by providing a layer of oil on the surface of the skin to prevent water evaporating from the skin surface. It is a very greasy moisturiser.
Liquid paraffin	Soften the ointment and reduce the viscosity of ointment

Emulsifying wax act as emulsifiers which actually work on a molecular level, by attracting both water and oil to different sites at the same time. Water is a polar material. Things that like water are also called polar materials. Polar materials are also called hydrophilic. Hydrophilic materials are water-loving materials. Non-polar materials like olive oil are hydrophobic. Hydrophobic means water fearing. An emulsifier has a hydrophilic portion and a hydrophobic portion. This essentially means that it can effective bind both water and oils. It means that some structures of the emulsifier attract oil, while others soak up water like a sponge. Each part traps the liquid keeping it from breaking free to separate. As an added bonus, because the oil remains mixed with the water, the wax actually helps the oil penetrate the skin, thereby replacing lost moisture. The large amount of liquid paraffin in the formulation produce the soft, more greasy and most spread of ointment. While the large amount of the emulsifying wax produce the hard, less greasy and less spreadibility upon application.

Conclusion

Different ointment composition will affect the physical property and the drug releasing rate from the ointment. Liquid paraffin had reduces the viscosity of the ointment made up of emulsifying wax. Higher proportion of emulsifying wax and lower proportion of liquid paraffin result with produce harder ointment with lower rate of drug release. Therefore, the ideal formulation of ointment to produce effective drug releasing rate should has the percentage of emulsifying wax, white soft paraffin and liquid paraffin at 30%, 50%, 20% respectively.

References

Michael E. Aulton. 2007. 3rd Edition Aulton’s Pharmaceutics : The Design And Manufacture of Medicines. Churchill Livingstone Elsevier

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

Martin, A.N. 2006. Physical Pharmacy: Physical Chemistry Principles in Pharmaceutical Sciences. Ed. Ke-5. Philadelphia: Lea & Febiger