Thursday, April 30, 2015

Assessment of the Effects of Different Compositions of Ingredients Used on the Characteristics of a Suspension Formulation

Title
Assessment of the Effects of Different Compositions of Ingredients Used on the Characteristics of a Suspension Formulation

Objective
 To study the effect of the composition of tragacanth on the texture, clarity and the colour of the suspension, the rate of sedimentation and viscosity of the suspensions of different compositions.

Introduction

A suspension is a type of disperse system where the insoluble solid particles are dispersed homogenously in the liquid phase. A good suspension must be in a homogenous form after shaking, easily poured from the container, has a uniform solid particle size and possess better texture and feel. Sediments that are formed upon storage have to be easily redispersed after shaking, forming homogenous suspension.
            In general, suspension comprises an active ingredient (solid phase) in a liquid carrier, a wetting agent, flavouring and colouring agents and preservatives. The function of a wetting agent such as tragacanth is to reduce the interfacial tension between the solid particles and the liquid. Suspension can be classified as a coarse suspension where the diameter of the particles is more than 1 µm or as a colloidal suspension where the particle size is less than 1 µm. In pharmaceutical practice, suspension is used to improve the stability of the active ingredient, taste, and bioavailability.


 Apparatus and Material

I. Apparatus
Weighing balance                                           
A set of pipette (1ml) and bulb-pipette
1 weighing boat                                              
1 centrifugation tube 15ml
A set of mortar and pestle                               
1 beaker 100ml
Plastic bottle 150ml                                       
 Centrifugation equipment
Measuring cylinder 50ml                                
 Viscometer                
A measuring cylinder 200ml                           

II. Materials
Chalk                                                               Syrup BP
Tragacanth                                                       Double-strength Chloroform Water
Concentrated Peppermint Water                      Distilled water


 Procedures

1.      A suspension of Paediatric Chalk Mixture (150ml) is prepared using the formulation below:
      
Chalk                                                                                       3g
Tragacanth                                                                    Refer to table below
Concentrated Peppermint Water                                           0.6mL
Syrup BP                                                                               15mL
Double Strength Chloroform Water                                      75mL
Distilled Water, q.s.                                                              150mL

Paediatric Chalk Mixture
Group
Tragacanth (g)
I
1, 5, 9
0.0
II
2, 6, 10
0.1
III
3, 7, 11
0.3
IV
4, 8, 12
0.5
Double Strength Chloroform Water
Tragacanth gum

Concentrated Peppermint Water
Syrup BP

Chalk




2.      Some of the suspension formed (5ml) is poured into the weighing boat and labelled. State and compare the texture, clearness and colour of the suspension formed.
3.      50ml of suspension formed is poured into the 50ml measuring cylinder and the height of the solid phase sediment in the cylinder is measured at intervals of 0, 5, 10, 15, 20, 25, 30, 40, 50 and 60 minutes.



4.      The remaining suspension (95ml) is poured into a 100ml beaker and viscosity of the suspension formed is determined using a viscometer.

5.      10ml of suspension is poured into a centrifugation tube and the height of the solid phase formed after centrifugation (1000rpm, 5 minutes, and 25°C) is determined.



Result and Discussion

1.      Compare the physical appearance of the suspension formed and explained.

Physical characteristic
Paediatric Chalk Mixture
I(group 1,5)
II(group 2,6)
III(group3,7)
IV(group4,8)
Texture
-smoothness
-viscosity
-redispersibility

+
++
+++
++++
+
++
+++
++++
++++
+++
++
+
Clarity
Less cloudy
Moderate cloudy
opaque
opaque
Colour
white
white
white
white
Layer
2 layer
1 layer
1 layer
1 layer

            From our observation, Suspension IV has the highest viscosity and has the smoothest appearance followed by Suspension III, II and I. This is due to highest amount of tracaganth added to the suspension IV. Tragacanth , a suspending agent where the chalk particles are dispersed more homogenously in suspension with higher amount of tragacanth. Thus a more smooth suspension will be formed by adding more tragacanth into suspension. Besides, tragacanth is partly soluble in water, in which it swells to gelatinous mass forms viscous solution with water. Due to this factor, higher amount of tragacanth will form more viscous solution such as Suspension IV.
            While,suspension I is the easiest to be redispersed followed by Suspension II, III and Suspension IV. This is due to deflocculated system formed after adding suspending agent to suspension. In a deflocculated system, the dispersed particles will remain as discrete units and settling will be slow. The slow rate of settling prevents entrapment of liquid within the sediment thus become compact and can be very difficult to be redispersed. The higher amount of tragacanth added, the particles will become more deflocculated. Flocculated system such as Suspension I will be more easily to be redispersed. It will lead to rapid rate of sedimentation, forming porous sedimentation. This structure of sedimentation will entrapped a large amount of the liquid phase which aid in redispersibility. Settling of particle is faster in Suspension I, supernatant quickly becomes clear compare to other suspension. Suspension IV will remain in the most cloudy form compare to other suspensions as the settling rate is slow.
            The colour of all suspensions formed is white. This is because of existence of chalk powder which is in white colour as it is dispersed throughout the suspension.



2. Graph UV absorption versus time.


The graph above shows the sedimentation height of a suspension (Pediatric Chalk Mixture type II) which is formulated with 0.5g Tragacanth powder. According to this graph, the suspension does not contain any sediment at the beginning of the experiment. However, as the time passes, sedimentation will start to form. This is because the forces of interaction between the inter–particular attractive forces are stronger than the inter-particular repulsive forces of the Tragacanth powder on suspension. From the time 0 to 55minutes, no precipitation can be observed on the suspension. The suspension was stable over period of 55minutes. On 55minutes and onward, increase in the height of precipitate was observed. Increase in the height of precipitate was record. From the graph above, the height of precipitation was 0 over a period of time. This probably caused by the amount of the suspending agent used in the suspension is enough to suspend the particle or drug for a longer time.


3.      Plot a graph of height of sedimentation against time for the formulations of suspension with different contents of Tragacanth. Discuss.

Time(min)
Average sediment height(mm) (X  SD)
0
5
10
15
20
25
30
35
40
45
50
55
60
Tragacanth contents(g)
0.0
47.50
±
67.1751
20
±
2.8284
16.5
±
6.3640
14.5
±
3.5355
14
±
2.8284
13.5
±
2.1213
13
±
1.4142
13
±
1.4142
13
±
1.4142
13
±
1.4142
13
±
1.4142
13
±1.4142
13
±
1.4142
0.1
11.95
±
0.07071
11.85
±
0.7071
11.7±
0.1414
11.6±
0.1414
11.6±
0.1414
11.45±
0.7071
11.3±
0.1414
11.2±
0.1414
11.05±
0.3536

11.0±
0.4243
10.9±
0.4243
10.35±
0.7906
10.15±
0.7906
0.3
0
±
0
4.5
±
6.3640
8
±
4.2426
8
±
4.2426

11
±
1.4142
11.5±
2.1213
19
±
8.4853
32
±
25.4558
32
±
25.4558
32
±
25.4558
34.5±
28.9914
34.5
±
28.9914
34.5±
28.9914
0.5
0
±
0
1.25±
0.3536
4.5
±
0.7071
8.5
±
0.7071
10
±
0
13
±
2.8284
16.5±
2.1213
18
±
2.8284
19.5±
2.1213
21
±
1.4142
21
±
1.4142
21
±
1.4142
21
±
1.4142

 
   The graph above shows the relationship of height of sedimentation with time in different suspension with different amount of tragacanth.  Based on the graph, the higher the tragacanth content, the greater amount of sediment formed. This is incorrect because theoretically, the height of sediment decreases as the weight of tragacanth increases. Thus, the suspension with higher tragacanth content should form less sediment. This is because tragacanth is a suspending agent to stabilize the suspension and reduce sedimentation by producing a deflocculated system. A suspension with ideal amount of tragacanth would be very stable, sedimentation rate slow and redisperse easily once shaken. The graph contains several errors which may be due to the following reasons: calculation mistakes, incorrect weighing of tragacanth, presence of impurities.


4. Describe briefly the mechanism of analysis of viscometer. Plot a graph of viscosity versus weight of Tragacanth (g). Give explanation.

Viscosity (cP)
1
2
3
4
5
6
Mean ± SD
Group 1
1.9
1.8
2.0
3.0
3.4
4.2
2.72 ± 0.89
Group 2
1.5
1.3
1.6
1.2
1.6
1.2
2.45 ± 0.36
Group 3
3.4
3.7
3.8
3.9
4.0
3.8
3.77 ± 0.47
Group 4
2.3
3.4
2.7
3.2
2.8
3.5
2.98 ± 1.03


Weight of Tragacanth (g)
0.0
0.1
0.3
0.5
Viscosity (cP) (Mean ± SD)
2.72 ± 0.89
2.45 ± 0.36
3.77 ± 0.47
2.98 ± 1.03




 A viscometer, also known as viscosimeter, is an instrument used to measure the viscosity and flow parameters of a fluid. There are many types of viscometers in the market and the type that we used in this experiment is the rotational viscometer. Viscometer operates by means of a cylinder or spindle that is immersed in a liquid. The cylinder or spindle undergoes retarding force due to the viscous drag of the liquid. The viscometer will then measure the additional torque required to maintain a constant speed of rotating to overcome the flow resistance. The higher the resistance, the higher the viscosity. The viscometer calculates the result and shows the value of viscosity in centipoise (cP) or milliPascal-second (mPa·s). 1 cP is equivalent to 1 mPa·s. A wide range of viscosity can be measured using viscometers with different types of spindles and speed ranges. Each spindle is categorized by different letter and number.

            In this experiment, we measured the viscosities of various suspensions. The suspensions varied in the weight of Tragacanth they contained, from the suspension without Tragacanth to suspensions containing 0.1 g, 0.3 g and 0.5 g of Tragacanth. Tragacanth, a natural polysaccharide, is a suspending agent which thickens the preparation. Therefore, the higher the weight of Tragacanth, the higher the viscosity of the suspension. Theoretically, the viscosity of the suspension is directly proportional to the weight of Tragacanth the suspension contains. Although we did not get a linear graph which we were supposed to get theoretically. This may be due to the error occur during the experiment. It was possible that there was an incomplete mixing of Tragacanth and chalk which caused the viscosity to be not uniform throughout the suspension. In addition, we were not sure which spindle size was the suitable one to be used in order to measure the viscosity of the suspension. The error may be due to the use of unsuitable spindle size. The viscometer we used also was malfunctioning for a short period of time before the lab assistant helped us. Thus the viscometer reading may also be inaccurate or inconsistent. Moreover, the errors can also arise from the improper cleaning of the spindle from previous use.


5. Plot a graph of height of ratio of sediment as a result of centrifugation vs. weight of Tragacanth. Give explanation.


Height (mm)
Group
1
2
3
4
Before centrifuge
80
80
80
80
After centrifuge
13
12
15
20
Ratio of height
0.1625
0.1500
0.1875
0.2500

Tragacanth composition (g)
0.0
0.1
0.3
0.5
Height ratio (_ X  ± SD)
0.1625
0.1500
0.1875
0.2500




From the graph we notice that there is a decrease of ratio of sedimentation from suspension I to II, and then there is an increase from suspension II to III and from III to IV. Theoretically, a hyperbola graph should be obtained. Ratio of sediment is influence by weight of Tragacanth. Ratio of sediment is decreasing slowly with increasing weight of Tragacanth. Suspension contains more Tragacanth is more stable. Therefore, the more higher the Tragacanth content, the lower the sediment formed.
Therefore the result of this experiment is not followed the theoretically result and this may be due to some error during the experiment or may be the tragacanth used is expired.


6.      Plot a graph of height of ratio of sediment as a result of centrifugation vs. weight of Tragacanth. Give explanation.

Amount of Tragacanth (g)
0.0
0.1
0.3
0.5
Ratio of height
1.67
0.36
5.64
0.11



    From the graph above, the ratio of height decreases as the amount of tragacanth increases. According to theory, the ratio of height of sediment is influenced by the weight of tragacanth. Ratio of height of sediment decreases slowly with increasing weight of tragacanth. Suspension that contains more tragacanth is more stable. Therefore, the higher the Tragacanth content, the lower the sediment formed. The result of the experiment is not accurate as the results do not shows exactly a gradual decrease in the ratio of height of sediment when the amount of tragacanth increases especially the error on experiment 0.3g tragacanth. This is most probably caused by the error when measuring the amount of tragacanth. The less amount of tragacanth cause the high height of sediment formed.  

Conclusion 

The rate of sedimentation and the height of sediment formed in the suspension depends on the amount of different Tragacanth powder used to form the suspension. When the amount of tragacanth powder increases, sedimentation rate will be more slowly and thus sediment height will be lower.The higher the amount of Tragacanth powder, the lower the height of sediment formed. This is due to the action of Tragacanth powder that prevent the solution from forming sediment.
            Conversely, low amount of tragacanth produces a coarser, more liquefied suspension. Clearer suspension resulted as solid phase will settle more rapidly. Thus stability of suspension will decrease. Redispersibility is easier for lower tragacanth amount.



References
1. Aulton, M.E.2002. Pharmaceutics: The Science of Dosage Form Design. Edinburgh: Churchill Livingstone.  
2. British Pharmaceutical Codex 1973
3.Pharmaceutical Practice, Winfield Richards, 2nd Edition

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