Tuesday, 20 May 2014

SUSPENSION

TITLE
Effects of different ingredients on the characteristics of suspension formulation

OBJECTIVES
To know the effects of using different amount of Tragacanth to the formulation of
Suspension.

INTRODUCTION
Suspension formulation is a type of dispersed system where the solid molecules do not dissolve homogenously in the liquid phase. In chemistry, a suspension is a heterogeneous fluid containing solid particles that are sufficiently large for sedimentation. Usually they must be larger than 1 µm. Suspension is classified as coarse suspension where the particle diameter is more than 1 µm or colloidal suspension where the particle size is less than 1 µm. In pharmaceutics, suspension is used to improve the stability, the taste and the bioavailability of the active ingredient. Unlike colloids, suspensions will eventually settle. Colloids and suspensions are different from solutions, in which the dissolved substance (solute) does not exist as a solid, and solvent and solute are homogeneously mixed. The physical stability of a pharmaceutical suspension is the condition in which the particles do not aggregate and in which they remain uniformly distributed throughout the dispersions. In order to achieve this ideal situation the suspension should have additive, which are added to achieve ease in re-suspension by a moderate amount of agitation.

 The internal phase (solid) is dispersed throughout the external phase (fluid) through mechanical agitation, with the use of certain excipients or suspending agents. Suspensions are classified on the basis of the dispersed phase and the dispersion medium, where the former is essentially solid while the latter may either be a solid, a liquid, or a gas.

A good suspension must stay in homogenous state after being shaken, be easy to pour out from the container and having a uniform solid particle size and also attractive taste and texture. Precipitation formed from the storage must be easily dispersed again after shaking and the dispersion formed must be homogenous.

Normally, suspension composed of active ingredient (solid phase) dispersed in the liquid carrier, wetting agent, flavoring agent and coloring agent. Wetting agent (eg: Tragacanth) is used to reduce the surface tension between solid particle and liquid. Suspending and thickening agents are added with the objective to increase apparent viscosity of the continuous phase thus preventing rapid sedimentation of the dispersed particles. The selection of the type and concentration of a suspending agent depends on sedimentation rate of dispersed particles, pourability and spreadibility. The ideal suspending agent should have a high viscosity at negligible shear, that is during shelf storage and it should have a low viscosity at high shearing rates which is it should be free flowing during agitation, pouring and spreadibility. A suspending agent that is thixotropic as well as pseudoplastic should prove to be useful as it forms a gel on standing and becomes fluid when shaken. They include natural polysaccharides (Acacia, Tragacanth), Semi-synthetic polysaccharides (Sodium Carboxymethylcellulose), Clays (Aluminium Magnesium Silicate) and synthetic agents (Carbomer). Pseudoplastic substances like tragacanth show these desirable qualities. In cases of combination use of suspending agents like bentonite and CMC dispersions are both pseudoplastic and thixotropic.

MATERIAL AND APPARATUS
Apparatus:                                                    
Weighing instrument                                      
Weighing boat                                                
Mortar and pestle                                           
150 ml plastic bottle                                       
50 ml measurable cylinder                             
200 ml measurable cylinder                           
1 set of 1 ml pipette and pipette bulb
1 centrifugator tube 15 ml
100 ml beaker
Centrifugator
Viscometer

Ingredients:
Chalk
Tragacanth
Concentrated Peppermint Water
Syrup BP
Double-strength chloroform water
Distilled water

PROCEDURE
1.      1 formulation of Pediatric Chalk Mixture (150 ml) was prepared by the following formulation.



Chalk                                                   3 g
Tragacanth                                           (referred to the Table 1)
Concentrated Cinnamon Water             0.6 ml
Syrup BP                                             15 ml
Double Strength Chloroform Water       75 ml
Distilled Water, q.s.                              150 ml

Table 1
Pediatric Chalk Mixture
Group
Tragacanth (g)
I
1, 5
0.0
II
2, 6
0.1
III
3, 7
0.3
IV
4, 8
0.5

2.      5 ml of suspension was poured into the weighing boat and was labeled. Texture, clarity and color of the suspension was described and compared.
3.      50 ml of suspension was poured into 50 ml measurable cylinder. Height of the solid phase precipitated in the cylinder was measured at the duration of 0, 5, 10, 15, 20, 25, 30, 40, 50 and 60 minutes.
Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
Height (mm)














4.      




4.  The rest of the suspension (95 ml) was poured into 100 ml beaker and the viscosity of the suspension was measured by a viscometer.
Reading
1
2
3
4
5
6
Viscosity






Mean + SD


5.      10 ml of suspension was poured into centrifugator tube and the height of the solid phase was measured after centrifugation (1000rpm, 5 minutes, and 25°C).


Height (mm)
Before centrifuged
After centrifuged
Height of ratio


RESULTS

Time (min)
Average height of sedimentation (cm) ( X ± SD)
0
5
10
15
20
25
30
35
40
45
50
55
60
Amount of tragacanth (g)
0.0

0
10
7
6
6
6
6
6
6
6
6
6
6
6
5
5
5
5
4
4
4
4
4
4
4
4
X
3.0
7.5
6.0
5.5
5.5
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
± SD
4.2
3.5
1.4
0.7
0.7
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.4
0.1

0
2
5
5
6
6
7
7
7
8
8
8
8
0
2
3
5
6
7
7
8
8
8
9
9
10
X
0.0
2.0
4.0
5.0
6.0
6.5
7.0
7.5
7.5
8.0
8.5
8.5
9.0
± SD
0.0
0.0
1.4
0.0
0.0
0.7
0.0
0.7
0.7
0.0
0.7
0.7
1.4
0.3
0
0.5
0.5
3
4
5
6
7
7
7
7.5
7.5
8
0
0
0
3
4
6
8
10
10
10
11
11
12
X
0.0
0.5
0.5
3.0
4.0
5.0
6.0
7.0
7.0
7.0
7.5
7.5
8.0
± SD
0.0
0.7
0.7
0.0
0.0
1.4
2.8
4.2
4.2
4.2
4.9
4.9
5.7
0.5

0
0
0
0
2
3
3
3
3
3
3
3
3
0
0
0
1
2
2
3
3
3
3
3
3
3
X
0.0
0.0
0.0
0.5
2.0
2.5
3.0
3.0
3.0
3.0
3.0
3.0
3.0
± SD
0.0
0.0
0.0
0.7
0.0
0.7
0.0
0.0
0.0
0.0
0.0
0.0
0.0


DISCUSSIONS
      1. Compare the physical appearance of the suspension formed and give the analysis.

Group
Tragacanth (g)
Texture
Clarity
Colour
1.
0.0
Smooth
Two layers are form. The above layer is clear whereas the bottom layer is cloudy
White
2.
0.0
Diluted
Cloudy
Opaque white
3.
0.1
Smooth, dilute
Initially, it is milky and not clear. After a time, it is cloudy and the suspended matter is visible
White and transparent above the white layer
4.
0.1
Smooth
Cloudy
White
         5.
0.2
Viscous
Cloudy
White
            6.
0.2
Smooth texture, viscous, not easy sediment
Cloudy
Milky white
         7.
0.3
Very viscous, slightly smooth texture
Cloudy
Milky
         8.
0.3
Smooth texture, more viscous
No sedimentation, cloudy
Milky white, one layer


         2.  Graph of sedimentation height versus time. (Suspension Formulation) Discuss the graph.

Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
Height (mm)
0
0.5
0.5
3
4
5
6
7
7
7
7.5
7.5
8



 

            The graph above shows the sedimentation height of a suspension (Pediatric Chalk Mixture type III) which is formulated with 0.3g Tragacanth powder. According to this graph, there is no sediment formed at the beginning of the experiment. This is because Tragacanth which used as suspending agent has stabilized the formulation from forming sedimentation and help in the formation of viscous suspension. It forms film around particle and decrease interparticle attraction.
       However, after the Periodic Chalk Mixture has been left to stand for a period of time, the sediment start to form and the height of sediment increase as the time increase. 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.  Particles in a suspension will settle out if the suspension is allowed to stand undisturbed. These particles can be redispersed when it is shaken and the sediment formed does not show decreased in height. This is due to the present of suspending agent. The addition of the tragacanth, at some critical concentration, negates the surface charge on the suspended particles and allows the formation of floccules or clusters as particles are held loosely together by weak van der Waals forces. Since the particles are linked together only loosely, they will not cake and may be easily redispersed by shaking the suspension.
    In addition, the height of sedimentation will increases with time until a maximum sedimentation level is achieved. The maximum sedimentation level is indicated by the constant level of height starting from 50 minutes till 60 minutes. This is due to the presence of tragacanth in the suspension which makes suspension III to become more stable. The greater the amount of suspending agent used, the longer the time taken for the sediment to form. Suspending agents capable to suspend the particles in the suspension which counteract the gravity force, thus forming a more stable suspension and prevent caking from happens.

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


Time (min)
Average height of sediment (mm) (x±SD)
0
5
10
15
20
25
30
35
40
45
50
55
60
volume of tragacanth (g)
0.0
3.0
±4.2
7.5
±3.5
6.0
±1.4
5.5
±0.7
5.5
±0.7
5.0
±1.4
5.0
±1.4
5.0
±1.4
5.0
±1.4
5.0
±1.4
5.0
±1.4
5.0
±1.4
5.0
±1.4
0.1
0.0
±0.0
2.0
±0.0
4.0
±1.4
5.0
±0.0
6.0
±0.0
6.5
±0.7
7.0
±0.0
7.5
±0.7
7.5
±0.7
8.0
±0.0
8.5
±0.7
8.5
±0.7
9.0
±1.4
0.3
0.0
±0.0
0.5
±0.7
0.5
±0.7
3.0
±0.0
4.0
±0.0
5.0
±1.4
6.0
±2.8
7.0
±4.2
7.0
±4.2
7.0
±4.2
7.5
±4.9
7.5
±4.9
8.0
±5.7
0.5
0.0
±0.0
0.0
±0.0
0.0
±0.0
0.5
±0.7
2.0
±0.0
2.5
±0.7
3.0
±0.0
3.0
±0.0
3.0
±0.0
3.0
±0.0
3.0
±0.0
3.0
±0.0
3.0
±0.0





The graph above shows the relationship between the height of sedimentation (mm) with time (min) for four different suspensions that contain different amounts of tragacanth (0.0g, 0.1g, 0.3g, 0.5g). The height of sediment decreases as the weight of the tragacanth increases.  Suspension which has more tragacanth is more stable because tragacanth acts as suspending agent. For formulation with optimum amount of tragacanth, the system is stable and no slow flocculation occurs. A good suspension is a suspension that have slow sendimentation process after the suspension is shaken. This is to ensure all the ingredient in suspension will disperse for a longer time to increase the efficiency of suspension administration.
From the graph, it shows that the more tragacanth content used, the less the sendiment formed with time for 0.1g, 0.3g and 0.5g of tragacanth content. However, for 0.0g of tragacanth content it shows initially highest sendiment rate which is 7.5mm and later become constant at 5.0mm. This might be because, initially the suspension does not have any suspending agent, and so that the suspension is not stable and it has very high sendiment, after that, sendiment rate become constant due to the some of the insoluble solid were dissolved in the solutions.

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



Amount of Tragacanth (g)
Readings
Viscosity (cP)
Viscosity (cP) (Average ± SD)
0.0
1
7.40
8.733 ± 1.124
2
9.40
3
7.70
4
9.50
5
8.20
6
10.20
0.1

1
7.00
6.583 ± 0.801
2
6.50
3
6.00
4
6.00
5
6.00
6
8.00
0.3
1
3.00
4.900 ± 1.221
2
4.70
3
5.90
4
4.00
5
5.90
6
5.90
0.5
1
13.20
12.967 ± 6.476
2
6.20
3
16.80
4
19.40
5
18.20
6
4.00































Equation:





Weight of Tragacanth (g)
0.0
0.1
0.3
0.5
8.733
6.583
4.900
12.967





Viscometer is a motor of viscometer that operates by rotating with the speed of 300rpm which is controlled by the central controller. The stirrer is rotated by disc that in turn moved by spring more than 180°. Besides, the change of rotation degree is directly proportional to the viscosity of the fluid and its rate of rotation. Infra red radiations emitted by LED is then diffuse through disc before detected by photo diod. Change in degree of disc rotation will influence the infra red radiation and this is detected and read by photo diod.
From the graph above, Suspension IV is the most viscous suspension compared to other suspensions formed. The more tragacanth added, the more viscous of the suspension being formed. According to theory, viscosity decreases from suspension IV to suspension I. The graph obtained should be linear where the viscosity of suspension is directly proportional to the amount of tragacanth. Chalk is suspended by tragacanth in the liquid phase and form suspension. When the amount of tragacanth is increased, suspension that forms will be more viscous. However, we do not obtain such graph because there are some mistakes in this experiment. For the value of suspension II and III in the graph, the values should be increasing instead of decreasing. This may due to the errors occur during the experiment.  The errors include insufficient amount of tragacanth added to suspension. Besides that, viscometer may not be cleaned appropriately after used. This may affects the reading of the viscometer.  Therefore, the viscosity graph of the suspensions obtained is different from theoretical graph.

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

Amount of Tragacanth (g)
Height (mm)
Height ratio
Height ratio (Average ± SD)
Before centrifuge
After centrifuge

Liquid phase
Solid phase
0.0
85
70
15
4.667
5.834 ± 1.650
80
70
10
7.000
0.1
82
62
20
3.100
5.300 ± 3.111
85
75
10
7.500
0.3
80
65
15
4.333
3.619 ± 1.010
82
61
21
2.905
0.5
77
68
9
7.556
5.334 ± 3.143
74
56
18
3.111

Equation:



Theoretically, increasing the amount of tragacanth will decrease the height ratio of sediment. It is based on function of tragacanth itself as suspending agent. Most of suspending agents accomplish two purposes. Suspending agents form film around particle and decrease interparticle attraction so prevent from coalescence. Besides, suspending agents also act as thickening agents. They increase in viscosity of the solution, which is necessary to prevent sedimentation of the suspended particles as per Stoke’s’s law.
A good suspension should have well developed thixotropic. At rest the solution is sufficient viscous to prevent sedimentation and thus aggregation or caking of the particles. When agitation is applied the viscosity is reduced and provide good flow characteristic from the mouth of bottle. Based on the graph above, as the amount of  tragacanth volume is increased, the height ratio is decreased until point of 0.3g of tragacanth, it start to increase again. So basically, this experiment is not correct because the graph show the increasing of height ratio. This could be because of some errors during handling this experiment. For example, make a mistake during measuring tragacanth or other substance. Or, it could be tragacanth itself not function normally because of interaction due to impuruities or the tragacanth is already affected during storage.

6.      What is the function of each material that is used in the suspension formulation? How is the use of different amount of Tragacanth affect the physical characteristic and stability of a suspension formulation?
The list of materials used in this suspension preparation are chalk, tragacanth, concentrated peppermint water, syrup BP, double-strength Chloroform Water and distilled water. Chalk functions as the active ingredient in this suspension preparation. Chalk also plays a role as an adsorbent that adsorbs excessive fluid in watery compound in order to make the compound becomes more solid and drier. Tragacanth acts as a thickening agent in the suspension preparation. Tragacanth also helps to increase the viscosity and the stability of a suspension preparation. Concentrated peppermint water functions as a flavouring agent that helps to mask an unpleasant taste and improves patient’s compliance. Syrup BP plays a role as a sweetening agent and a flavouring agent. Double-strength Chloroform Water plays a role as a preservative, which helps the suspension preparation to become infavourable to microbial growth. Distilled water is used as a vehicle and a bulking agent in this suspension preparation. The usage of the different concentration of tragacanth can influence the texture, clarity and the colour formed in the suspension preparation. Based on the results obtained on the texture, clarity and colour of the suspension formed, when the amount of tragacanth used increases, the viscosity of the suspension increases. This shows that when the viscosity of the suspension increases, the suspended particles take a longer time to separate from the vehicle and form two layers. Moreover, when the amount of tragacanth increases, the colour of the suspension preparation becomes more milky white. This shows that the suspension preparation has a higher stability with the increase of the amount of tragacanth used. 

Group 1 and 2 do not use any tragacanth in their suspension preparation. Thus, the suspension preparation has a diluted, smooth texture and less viscous. The suspension also forms two layers very easily and the colour is white. This shows that there is no suspending or also known as thickening agent, which aids in the viscosity and the stability of the suspension formed. When the amount of tragacanth added to the suspension preparation increases, the texture of the suspensions become more viscous and also smooth. The suspension preparation also does not sediment easily. This shows that the tragacanth acts as a suspending agent which increases the viscosity and the stability of the suspension preparations. The tragacanth also acts as a thickening agent which causes the suspension preparation to become more milky white in colour as the amount of tragacanth used increases.

CONCLUSION

            For the experiment, we conclude that different amount of tragacanth will give different characteristic effect of suspension. The higher the amount of tragacanth used, the lower the height of sedimentation. Theoretically, increasing the amount of tragacanth used will increase the viscosity of suspension. However from this experiment, due to some errors, the viscosity decreased as amount of tragacanth increase, only upon 0.3g of tragacanth, the graph showed increasing on viscosity.

REFERENCES




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