Thursday, 18 April 2013

EXPERIMENT 2: Assessment on the Effect of Different Content Materials on the Characteristics of a Suspension Formulation

Objectives:
The objective of this experiment is to study and evaluate the effects of different content materials on the physical characteristics of the formed suspension.


Introduction
Suspension formulation is a type of dispersed system where the solid molecules do not dissolved homogenously in the liquid phase. A good suspension must stay in the state of homogenous 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 shaken 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 (ex: Tragacanth) is used to reduce the surface tension between solid particle and liquid. 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.
Paediatric Chalk Mixture is a type of antacid preparation use to treat diarrhoea. The materials that made up this suspension are such as chalk, tragacanth, concentrated cinnamon water, syrup BP, double strength chloroform water and distilled water. It is a suspension formulation thus patients must shake the bottle before using this preparation.


 Apparatus

Weighing balance                               1 1ml pipette and pipette bulb
1 weighing boat                                  1 15 ml centrifuge tube
1 set of mortar and pestle                   1 100ml beaker
1 150ml plastic bottle                         Centrifugator
1 50ml measuring cylinder                  Viscometer
1 200ml measuring cylinder
           
Materials

            Chalk                                                   Syrup BP
            Tragacanth                                           Double-strength chloroform water
            Concentrated peppermint water            Distilled water


Procedures and Results

  1.      A formulation of Paediatric Chalk Mixture suspension (150 mL) is prepared by using this formula:


Table 1
Paediatric Chalk Mixture
Group
Tragacanth (g)
1
5
0.0
2
6
0.1
3
7
0.3
4
8
0.5
  
2.  A little suspension formed (5 mL) is poured into a weighing boat and labelled. The texture, clarity and colour of the suspension formed is compared and explained.

Group / Comparison
Texture
Clarity
Colour
5
More dilute
Clear
Cloudy
6
Dilute
Not clear
Milky, chalky
7
Concentrated
Opaque
White
8
More concentrated
Highly opaque
White


3. 50ml suspension was poured into a 50ml measuring cylinder and the height of sediment formed in the cylinder is measured at interval of 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 and 60 minutes.

Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
Height (mm)
0
18
15
12
11
10
10
9
9
9
9
9
9





4.      The rest of the suspension (95 ml) was poured into 100 ml beaker and the viscosity of the suspension was measured by the viscometer.

When the Tragacanth used is 0.0g

Reading
1
2
3
4
5
6
Viscosity (cP)
0
0
2
2
2
3.5
Average + SD
1.583 ± 1.3571


When the Tragacanth used is 0.1g

Reading
1
2
3
4
5
6
Viscosity (cP)
2
2
2
3
2
3
Average + SD
2.333 ± 0.5164

When the Tragacanth used is 0.3g

Reading
1
2
3
4
5
6
Viscosity (cP)
2.5
1.5
2
2.5
3
3.5
Average + SD
2.5 ± 0.7071

When the Tragacanth used is 0.5g

Reading
1
2
3
4
5
6
Viscosity (cP)
0
10
5.5
3
3
3
Average + SD
4.083 ± 3.3825


Weight of Tragacanth (g)
0.0
0.1
0.3
0.5
Viscosity(x ± SD)
1.583±1.3571

2.333±0.5164
2.5±0.7071

4.083±3.3825


5.      10ml of the suspension was poured into a centrifuge tube.Then,the height of sediment is determined after centrifugation.(1000rpm, 5 minutes, 25°c)

Discussion

1.      Compare the physical appearance of the suspensions that formed.

The texture of the solution become more concentrated which directly proportional to the amount of tragacanth that had been added. When amount of the tragacanth is zero, the clarity of the solution is very clear due to absence of suspending agent and the chalk will sediment drastically in high sedimentation rate compare to the other solutions which the clarity is decrease with the increasing amount of tragacanth. The higher amount tragacanth cause the suspension look highly opaque due to low sedimentation rate of suspensoid. Colour of suspension become white when high amount of suspending agent present in the solution. Suspending agents causing disperse element become suspense in long duration and homogenous white colour can be directly observed.

2.      Plot a graph of height of sediment vs. time. Give explanation.

Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
Height (mm)
0
18
15
12
11
10
10
9
9
9
9
9
9






The graph above is the formation of sediment for formulation I. Sediment starts once the time started to count.With increasing the time, the height of the sediment decrease as time goes,the sediment arrange themselves closer to each other thus forming a more compact sediment.Sedimentation occurs due to the gravitational forces in which comparatively large drug particles will be sedimented. The height of the sediment becomes constant when all the chalk particles are sedimented.

3.      Plot a graph of height of sediment vs. time for the formulation of suspension that contain varied amount of Tragacanth. Give explanation.

Time (minutes)
Height of sediment (mm)
0
5
10
15
20
25
30
35
40
45
50
55
60
Amount of Tragacanth powder (g)
0.0
0
18
15
12
11
10
10
9
9
9
9
9
9
0.1
0
3
3
4
5
5
5
5
5
5
5
5
5
0.2
0
2
4
6
7
8
8
9
9
10
10
10
10
0.3
0
1
3
7
11
15
18
20
20
21
21
21
21




For suspension without tragacanth, the height of sedimentation increases sharply to 18mm within 5 mintues. However, it decreases gradually after 5 minutes. This is due to the absence of tragacanth which is the suspending agent. The particles tend to concentrate and flocculate, eventually the sediment aggregate and form a compact cake at the bottom of cylinder. During the sedimentation, the smaller particles tend to fill in the spaces available between larger particles. As the time goes on, the spaces between particles are fully filled by the smaller particles and no more spaces are available. This explains the height of sediment remains the same after 35th minutes.
For suspension with 0.1g tragacanth added, the height of sediment increases slowly until it reach a plateau of 5mm height at 20th minutes. This occurs because of the tragacanth which is the suspending agent acts by increasing the viscosity of dispersion medium. But this little amount is not enough to support the dispersed phase for long period. Hence, sediment starts to form at 20th minutes.
For suspension with 0.2g tragacanth added, the height of sediment increases gradually within 40 minutes. At 45th minutes, the sediment of 10mm height only starts to form. This is due to the higher amount of suspending agent compared to the suspension above. The greater the amount of suspending agent, the more stable the suspension is.
For suspension with 0.3g tragacanth added, the height of sediment increases merely 1mm in 5 minutes time. However, it increases greatly to 21mm at 45th minutes. The dispersed phase actually remains suspended during this period. There is no caking occurs due to the high amount of tragacanth powder.


4.      Describe briefly the mechanism of viscometer. Plot a graph of viscosity vs. weight of Tragacanth. Give explanation.




 The viscometer is used to measure the viscosity of the suspension. It operates by the motor which rotates with the speed of 300rpm. This rotation is controlled by the central controller. It has a stirrer which is rotated in operation and the rotation is controlled by disc which is moving by spring at more than 180 degree. The change of rotation degree and the rate of rotation is closely linked to the force of rotation by the disc and it is measured as current. The change od rotation of degree is directly proportional to the viscosity of the fluid and the unit is measured as cP. Besides, the infra red radiations are emitted by LED and these radiations diffuse through disc and then they  are detected by photo diod. Change in degree of disc rotation will influence the emitting infra red radiations and the changes are detected and read by photo diod.
Tragacanth used in the formulations acts as the suspending agent which is used to reduce  the surface tension and prevent clumping and allows redispersion. Also, tragacanth acts as the thickening agent due to its thixothropic property. Hence, it imparts the viscosity to the suspension. Higher the content of tragacanth used, higher the viscosity of the suspension. This can be shown in our result. Theoretically, the graph obtained should be linear as the increasing of the viscosity versus the content of tragacanth should be in proportional manner. However, non-linear graph is obtained. This may be due to some errors happened in the experiment. For examples, there are presence of foreign particulate matters in the suspension and the happening of technique errors when measuring and reading the cP value.

Weight of Tragacanth (g)
0.0
0.1
0.3
0.5
Ratio of height ( x ±SD)
7.00±5.07
11.00±5.07
17.00±5.07
20.00±5.07






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



From the result above, we can see that when the weight of the tragacanth increase, the ratio of the height of sediment will increase as well. In the experiment , we have found that the height of sediment have decrease with the weight of the tragacanth. When the weight of tragacanth increase, the height of the sediment will decrease. The formation of the sediment is due to the instability of the suspension, the suspension that contain more tragacanth will be more stable and less sediment will be formed after centrifugation while the suspension with less tragacanth will be less stable and more sediment will be formed after the centrifugation. Tragacanth is a suspending agent that can increase the viscosity of the solvent and thus the solvent can hold the suspended particles from settle down for a longer time and thus it is more stable.


6.      What are the functions each of the materials that have been used in suspension’s formulation? How different concentration of tragacanths can affect the physical characteristics and stability of the suspension’s formulation.

Chalk (active ingredient) as adsorbent which not mix well with watery elements. The major function of this active ingredient is to treat diarrhea. 
Tragacanth (thickening agent)  viscous in nature, it provides thixotrophy to the solution. They increase in viscosity of the solution, which is necessary to prevent sedimentation of the suspended particles as per Stoke’s’s law. Besides acting as a suspending agent, they also impart viscosity to the solution. It is a better thickening agent than acacia. A good suspension should have well developed thixotropy. 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.The physical stability of suspension was mainly dependent on the type of suspending agent rather than the physical characteristics of the drug.
Concentrated cinnamon water (flavouring agents) added to increase patient acceptance. The four basic taste sensations are salty, sweet, bitter and sour. It has been proposed that certain flavours should be used to mask these specific taste sensations.
Syrup BP (flavouring agents) employed as a base for medicinal purposes consists of a concentrated or saturated solution of refined sugar in distilled water which is thick, viscous liquid consisting primarily of a solution of sugar in water, containing a large amount of dissolved sugars but showing little tendency to deposit crystals. The viscosity arises from the multiple hydrogen bonds between the dissolved sugar, which has many hydroxyl (OH) groups, and the water.  Technically and scientifically, the term syrup is also employed to denote viscous, generally residual, liquids, containing substances other than sugars in solution.
Double strength chloroform water (preservative) is included in pharmaceutical dosage form to control the microbial bio burden of the formulation. Ideally, preservatives should possess a broad spectrum of antimicrobial activity encompassing Gram-positive and Gram-negative bacteria and fungi, be chemically and physically stable over the shelf-life of the product ,have low toxicity, should not be adsorbed on to the container, should be compatible with other formulation additives and its efficacy should not be decreased by pH.The naturally occurring suspending agents such as tragacanth, acacia, xanthan gum are susceptible to microbial contamination. If suspension is not preserved properly then the increase in microbial activity may cause stability problem such as loss in suspending activity of suspending agents, loss of colour, flavour and odour, change in elegance etc. Antimicrobial activity is potentiated at lower pH. 
Distilled water (vehicle) which is as vehicle to carry all the active ingredients in the pharmaceutical suspensions into patient’s bodies. The principle of using water in healing and renewing the body has been well known from early history. Distilled water is the purest water that can assist in healing process. Higher concentration of tragacanth cause more opaque, more viscous and more difficult to sediment. For stability, higher concentrations of tragacanth lead to more stable suspensions. But too high viscosity is not good in suspension formulation as when it sediment, it not easily to re-disperse even after we put effort in shaking the suspension, and then finally cause imbalance and inaccurate dosing. This will lessen the therapeutic effect of the drug preparation itself.

Conclusion:
As a conclusion, the assessment here showed that the different composition in the formulation will affect the physical property of the suspension.

  
References:

1 comment:

  1. Do u all think that 60 minutes are enough for all the insoluble solutes to sediment?

    ReplyDelete