Sunday, April 28, 2013


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

OBJECTIVE

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
   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.















RESULTS AND DISCUSSION

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


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