It is a wise mans part, rather to avoid sickness, than to wishe for medicines. ~Thomas More, Utopia

It is a wise mans part, rather to avoid sickness, than to wishe for medicines. ~Thomas More, Utopia
It is a wise mans part, rather to avoid sickness, than to wishe for medicines. ~Thomas More, Utopia

Friday, 23 May 2014

EXPERIMENT 4: ASSESSMENT OF THE IMPACT OF DIFFERENT CONTENT ON THE PROPERTIES OF AN OINTMENT FORMULATION


OBJECTIVES
1) To know the effects of different ointment formulation on the physical characteristic of the ointment.
2) To determine the effects of different ointment formulation on the rate of release of drug from the formulation.

INTRODUCTION
Ointment formulation is a semisolid medicinal preparation usually having a base of fatty or greasy material. It is homogeneous, viscous and thick oil (oil 80% - water 20%) with a high viscosity. Ointments are used topically for several purposes, e.g., as protectants, antiseptics, emollients, antipruritics, kerotolytics, and astringents. The vehicle or base of an ointment is of prime importance if the finished product is expected to function as any one of the above categories. In the case of a protective ointment, it serves to protect the skin against moisture, air, sun rays and other external factors. It is necessary that the ointment neither penetrates the human skin barriers nor facilitates the absorption of substances through this barrier. An antiseptic ointment is used to destroy or inhibit the growth of bacteria. Frequently bacterial infections are deeply seated; a base which has the capacity to either penetrate or dissolve and release the medication effectively is therefore desired. Ointments used for their emollient effect should be easy to apply, be non-greasy and effectively penetrate the skin.
Ointments can be prepared either by mechanical trituration or by fusion methods. Irrespective of the method employed for the preparation, ointments should be smooth and free from granular or gritty particles. For trituration, in this 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. The ingredients are melted together in descending order of their melting points and stirred to ensure homogeneity in fusion.
Ointment bases, as described, may by used for their physical effects or as vehicles for medicated ointments. Each ointment base type has different physical characteristics and therapeutic uses based upon the nature of its components. The different formulation of ointment will affect the texture and physical characteristics of ointment and the rate of the drug release from the formulation to target site. Properties which affect choice of an ointment base include stability, penetrability, solvent property, irritant effects and ease of application and removal.


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 kuvet
Spectrophotometer UV/Vis

Ingredients:
Emulsifying wax
White soft paraffin
Liquid paraffin
Acetylsalicylic acid
Distilled water

Procedure:

  1. 50g of Emulsifying Ointment was prepared for 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

  1. 5 g of cream was taken and put into the weighing boat and was labeled. The texture, clarity and the color of the cream was described and compared.
  2. 1.5 g of Acetylsalicylic acid powder was incorporated into 30 g of cream which was prepared by levigation technique.
  3. Acetylsalicylic acid was filled into the dialysis bag and the two side of the bag was tied.
  4. The bag was put into a beaker (200ml) filled with distilled water (100ml) which was heated to 37°C.
  5. Every 5 minutes, one aliquot sample (3 – 4 ml) was pipette and the release of Acetylsalicylic acid from the cream base was determined by using spectrometer UV-visible. The distilled water was stirred with glass rod before the sample was taken.

RESULT : 
3.

TIME(MIN)
AVERAGE OF UV ABSORPTION AT 300 NM (x ± SD)

0
5
10
15
20
25
30



Emulsifying oinment
I
0.0225 ± 0.0075
0.062 ± 0.006
0.066 ± 0.01
0.0945 ± 0.0005
0.1105 ± 0.0015
0.159 ± 0.031
0.139 ± 0.018
II
0.049 ± 0.024
0.285 ± 0.165
0.316 ± 0.176
0.3535 ± 0.1735
0.398 ± 0.155
0.422 ± 0.159
0.451 ± 0.165
III
0.037 ± 0.002
0.041 ± 0.001
0.0795 ± 0.0335
0.078 ± 0.023
0.11 ± 0.052
0.127 ± 0.065
0.1545 ± 0.0845
IV
0.0815 ± 0.0185
0.152 ± 0.031
0.218 ± 0.006
0.225 ± 0.0015
0.2285 ± 0.0065
0.267 ± 0.027
0.321 ± 0.01




TIME (MIN)
UV absorption

0
5
10
15
20
25
30

UV absorption at 310nm
0.073
0.120
0.140
0.180
0.243
0.263
0.286

Discussion:
1. Comparison of the physical appearance of the each ointment.
Group
Texture
Clarity
Colour
Spreadibility
Greasiness
     Hardness
5
+
Least greasy
++++
Turbid
Chalky white
6
++
Relatively greasy
+++
Turbid
Chalky white
7
+++
Greasy
++
Turbid
Slightly light white
8
++++
Most greasy
+
Turbid
Light white


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


From this experiment, distilled water filled in the beaker represents the blood circulation in the body. Since distilled water is hypotonic so acetylsalicylic acid inside the dialysis bag can diffuse out from it. Hence, acetylsalicylic acid will diffuse out to the hypotonic solution against concentration gradient.  As a result, the content of acetylsalicylic acid in the distilled water increases. Dialysis bag acted as phospholipid bilayer and this experiment is conducted in 37ºC because the temperature is setted up as human body temperature. The UV absorption value obtained from the spectrophotometer represents the amount of acetylsalicylic acid released from the ointment in the dialysis bag into the distilled water in the beaker.
Based on the graph above, the greater the time taken the greater UV absorption of ointment. This is because the released of acetylsalicylic acid of ointment from the dialysis bag in the beaker increases as time increases. This shows that the absorption of the formulation is increases in a longer period of time and decreases as the ingredients in the formulation is getting lesser. This means that amount of acetylsalicylic acid in the distilled water increases with time. The gradient of the graph represents the rate of drug (acetylsalicylic acid) release to the blood circulation (distilled water). When the UV absorption value increases, the acetylsalicylic acid release from the dialysis bag into the surrounding solution also increases.
3.

TIME(MIN)
AVERAGE OF UV ABSORPTION AT 300 NM (x ± SD)

0
5
10
15
20
25
30



Emulsifying ointment
I
0.0225 ± 0.0075
0.062 ± 0.006
0.066 ± 0.01
0.0945 ± 0.0005
0.1105 ± 0.0015
0.159 ± 0.031
0.139 ± 0.018
II
0.049 ± 0.024
0.285 ± 0.165
0.316 ± 0.176
0.3535 ± 0.1735
0.398 ± 0.155
0.422 ± 0.159
0.451 ± 0.165
III
0.037 ± 0.002
0.041 ± 0.001
0.0795 ± 0.0335
0.078 ± 0.023
0.11 ± 0.052
0.127 ± 0.065
0.1545 ± 0.0845
IV
0.0815 ± 0.0185
0.152 ± 0.031
0.218 ± 0.006
0.225 ± 0.0015
0.2285 ± 0.0065
0.267 ± 0.027
0.321 ± 0.01







Based on the graph above, the average UV absorption for each formulation increases with time as the concentration of acetylsalicylic acid in the beaker is increases. In every interval of 5 minutes, 3ml of content in the beaker were taken rendering a progressive decrease in amount of solution in the beaker. The active ingredient in the ointment was being released into the solution in the beaker from time to time. Thus, the concentration of the active ingredient- acetylsalicylic acid increases progressively which is indicated by an increase in the average UV absorption.
The standard deviation for formulation is quite normal. The deviation are might due to some errors occurred throughout the experiment. The series 3 shows a more consistent value compared to other series while the value of standard deviation for series 2 and 4 is still acceptable.
Drug diffusion of emulsifying ointment is affected by the formulation of emulsifying wax and liquid paraffin. Theoretically, drug diffusion of emulsifying ointment 4 is the most followed by emulsifying ointment 2, 3 and the drug diffusion of emulsifying ointment 1 is the least. The more the emulsifying wax, the more the drug will be diffuse out. This is shown in the graph above.




4. What is the function of each ingredient that is used in the ointment? How the different composition of the emulsifying wax and liquid paraffin affects the physical properties of the ointment and the release rate of a drug from it?
Emulsifying wax acts as an emulsifying agent that 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 is an ointment base which is used as an emollient and moisturizer. To increases the greasiness of the ointment so that it can penetrate through the skin hydrophobic lipid bilayer more easily. In this experiment, to aid the diffusion of acetylsalicylic acid from the dialysis bag.
Liquid paraffin acts as the base too. It softens the ointment formed. It also decreases the ointment viscosity and acts as emollient.
When the proportion of the emulsifying wax decreases and liquid paraffin increases, the spreadibility and greasiness of the ointment increase while the hardness decreases and thus the drugs can be released from the formulation and penetrate through the skin lipid bilayer more readily. Therefore, the rate of release of drug increases. However, this is different from results of formulation IV which may be due to the experiment errors such as the distilled water is not stirred before sampling. So, ideally, the formulation IV should have the highest rate of release.

Conclusion
From the compounding, our ointment is spreadable, relatively greasy, hard, turbid and chalky white in colour. From the graph of UV absorption against time, it is shown that the absorption of the formulation is increases with time and then decreases as the contents of ointment is getting lesser. We can conclude that the larger amount of the emulsifying agent, the faster the diffusion of ointment.

Reference
i. Ointments: Preparation and Evaluation of Drug Release. UNC. http://pharmlabs.unc.edu/labs/ointments/prep.htm
Retrieved on: 19/5/2014

ii. Allen. 9th edition. Ansels’s Pharmaceutical Dosage Form and Drug Delivery System. Chapter10. Wolter Kluwer

iii. UV absorption spectrometry. http://teaching.shu.ac.uk/hwb/chemistry/tutorials/molspec/uvvisab1.htm
Retrived on: 20/5/2014

iv. Visible and Ultraviolet Spectroscopy. http://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/spectrpy/uv-vis/spectrum.htm
Retrived on: 20/5/2014




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