Monday, 29 April 2013

SUSPENSION REPORT



EXPERIMENT 2 :EFFECT OF DIFFERENT INGREDIENTS ON CHARACTERISTICS OF SUSPENSION FORMULATION


OBJECTIVE
To know the effects of using different amount of Tragacanth to the formulation of suspension.


INTRODUCTION

          Suspensions are solid dispersion of insoluble or sparingly-soluble drugs in aqueous or oily vehicles. They are intended for oral administration, topical application or parenteral administration of drugs. Suspension of drugs for oral administration is an easy way to administer insoluble, or sparingly soluble drugs to infants and elderly who have difficulty in administering drugs in tablet or capsule forms. It also allows rapid absorption of some insoluble drugs, which are slowly absorbed from tablet dosage form, such as griseofulvin.

          Furthermore, suspension is able to mask the unpleasant taste of drug. It is also suitable for drugs that are chemically unstable in solution but stable when suspended.  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. Suspension should also has attractive taste and texture. Precipitation formed from the storage must be easily dispersed again after shaking and the dispersion formed must be homogenous. They must also be chemically stable and therapeutically efficient. In short, suspension is used to improve the stability, the taste and the bioavailability of the active ingredient.

            Suspension requires excipients, such as wetting agent, flavouring agent and colouring agent. Wetting agent (eg: 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. Suspension should be shaken before used and they should be stored in tight containers, protected from extreme temperature and light.


APPARATUS AND MATERIALS

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





PROCEDURES



1. Pediatric Chalk Mixture (150mL) formulation of suspension is prepared by using formula as followed :


Chalk
3g
Tragacanth
0.1g
Concentrated peppermint water
0.6mL
Syrup BP
15mL
Double-strength Chloroform water
75mL
Distilled water, q.s.
150mL



2. 5mL of suspension formed is poured into a weighing boat and is labeled. The suspension formed is elaborated and compared its texture, clearance and also color.



3. 50mL of suspension formed then is put into 50mL of measuring cylinder and the height of sediment solid is measured on 0, 5, 10, 15, 20, 25, 30,40,50, and 60 min.

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




















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


Reading
1
2
3
4
5
6
Viscosity






Mean + SD






5. 10mL of the suspension is poured into a centrifuge tube and the height of sediment solid after centrifuged is determined. (1000 rpm, 5 minutes, 25˚C)



Height (mm)
Before centrifuged
80
After centrifuged
20
Height of ratio
80:20





RESULT AND DISCUSSION

1. Compare the physical characteristics of the suspension formed and give comments.

       Suspension
                Texture
                  Appearance
           Colour
         I
       Less viscous
     Slightly cloudy, 2 layers
    Slightly milky
        II 
          Viscous
    Moderate cloudy
    Milky
       III
      More viscous
    Cloudy
    Milky white
       IV
      Most viscous
    Cloudy
    Milky

          From the results, there is an increase in the viscosity from suspension I to suspension IV. This is due to the addition of increasing amount of tragacanth gum from suspension I to IV. Viscosity of suspension I is very low as there is no tragacanth added into the formulation, hence, this causes it to be more easily spread (re-disperse) while the viscosity of the suspension IV is the highest, causing it more difficult  to spread. Therefore, the Formulation II, III and IV contain tragacanth which makes the texture of suspension become more viscous. The suspension is getting more viscous when the weight of tragacanth used increased. Tragacanth will increase the viscosity of the suspension. Therefore, the suspension should be shaken by a strong force to be homogeneous.

          All the suspensions are cloudy. The amount of tragacanth determine the uniformity in the distribution phase of a suspension. In the suspension I, it was obvious that there are two phases (phase precipitate and the liquid phase), in which the solution is slightly cloudy and give the suspension milky colour. This is due to the presence of particles or white powder that are not uniformly dispersed in it. For suspension II, the particles spread more uniformly if compared to suspension I, causing it is to appear moderately cloudy and having a milky colour. Both suspensions III and IV were homogenous suspension when compared with suspension I and II. They are more cloudy and the colour is milky too. All the suspensions are cloudy and white in colour. This is due to the dispersion of the insoluble chalk particles in the solution.            

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

Time (min)
0
5
10
15
20
25
30
35
40
45
50
55
60
Height (mm)
0
1
2
2.5
3
3
3
4
4
4
4
4
4




          The graph above shows the sedimentation height of a suspension (Pediatric Chalk Mixture type II) which is formulated with 0.1g 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. Hence, 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 35 minutes till 60 minutes. 


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

          




For suspension 1 (without tragacanth), there is a sharp increase in height of sedimentation from 0 to 10 minutes, followed by a constant level of height as time proceeds. The sharp increase is due to the absence of tragacanth. Particles tend to regroup, to flocculate and they are held by van der Waals forces. Therefore, the content settles to the bottom quickly. Based on the theory, the height of sedimentation supposingly should decrease as time proceeds longer. This is because the particles filled in the spaces between the porous structures to make the sediment become more compact. The sediment forms a cake at the bottom of the measuring cylinder. In compacted cake, stronger forces are involved. However, from our experiment result, the height of sedimentation increases initially, followed by a constant level of height as time goes by. This may be due to the very small changes in height that is difficult to be identified and measured. As such, the decrease in height is difficult to be determined.

         For suspension 2 (with 0.1g of tragacanth), there is an increase of height of sediment from 0 to 35 minutes, followed by a constant level of height from 35 to 60 minutes. However, compared to suspension 1, the rate of sedimentation of suspension 2 is slower. This is because of the presence of tragacanth makes the active ingredients suspended in the suspension. As time passes from 35 to 60 minutes, the height of the sediment remains constant, similar to the graph in the suspension 1. However, based on theory, the height of sediment supposingly should be slightly decreased as time proceeds longer. This is due to the filling of spaces between the porous structures which in turn makes the sediment to become more compact and forms cake at the bottom of the measuring cylinder as some crystals knit together at point of contact at the bottom of the container. 

For suspension 3 (with 0.3g tragacanth), the height of the sediment increases slowly and remains constant from 40 to 60 minutes. This is due to the presence of tragacanth in the suspension which makes suspension 3 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.

For suspension 4 (with 0.5g tragacanth), there is sediment observed as early in 5 minute. Then, the height of the sediment increases dramatically from 5 to 50 minutes. The height of the sediment then remains constant from 55 to 60 minutes. The result of our group was inaccurate. This is because with a high amount of tragacanth, the particles remain suspend in the suspension which counteract the gravity force, thus there is suppose no caking of suspension. The suspension should be said to be stable. So based on this theory, it should no formation of sediment in first 5 to 30 minutes. The result taken from our group maybe due to the some errors, in which the people conducting the experiment do not know the proper way of measuring the sediment, or difficult in determining the sediment due to no obvious colour difference, and the tragacanth use maybe expired and thus has lower effect to the suspension.



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
2.50
1.50
1.50
1.0
2.0
2.5
1.83 ± 0.55
Group 2
5.00
5.00
5.00
5.00
5.00
5.00
5.00 ± 0.00
Group 3
0.00
0.00
6.00
6.00
12.00
12.00
6.00 ± 4.90
Group 4
20.00
18.50
17.50
16.50
16.50
17.00
17.67 ± 1.25



Weight of Tragacanth (g)
0.0
0.1
0.3
0.5
Viscosity (cP) (Mean ± SD)
1.83 ± 0.55
5.00 ± 0.00
6.00 ± 4.90
17.67 ± 1.25




          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 the graph we obtained shows that increased weight of Tragacanth increases the viscosity of the suspension, 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.

Amount of Tragacanth (g)
0.0
0.1
0.3
0.5
Ratio of height
11.43
6.67
5.33
4.00



          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 considered accurate as the results shows a gradual decrease in the ratio of height of sediment when the amount of tragacanth increases.





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?



Chalk is an adsorbent and antacid.  It is also an active ingredient used in the treatment of diarrhea.



Tragacanth is used as a suspending agent to reduce the cohesion between solid and liquid particles of aqueous medium. The amount of Tragacanth used will affect the physical properties of the suspension. Higher amount of Tragacanth will produce a suspension which is smoother. Suspension containing Tragacanth is stable but on prolonged storage it is hard to redisperse, while suspension without Tragacanth has low stability and will form sedimentation rapidly but is easy to redisperse.



Concentrated Cinnamon Water is used as flavoring agent that give carminative effect for the suppositories.



Syrup BP is used as diluents and also sweetening agent. It increases the viscosity of the suspension and acts as sweetening agent to mask the unpleasant taste so that the compliance of the patient is increased. Syrup will affect the viscosity of the suspension formed as it is a viscous liquid. Suitable amount of syrup should be used to produce suitable viscosity of the suspension formed.

Viscosity of the suspension will affect the physical stability and the rheological characteristic of the suspension. This is to avoid the rheological problem in which the suspension is maybe hard to pour out from the container. Syrup content should also be taken care for diabetes patients.



Double Strength Chloroform Water is used as preservative to prevent microbial growth. It also give some flavouring.

Distilled water is used as diluents to give aqueous medium.



CONCLUSION

          The higher the amount of tragacanth, the slower is the rate of sedimentation. Besides, the higher the quantity of tragacanth, the higher is the viscosity of suspension. The ratio of height of sedimentation decreases with an increase in weight of tragacanth.




APPENDIXS


These are the materials and apparatus needed to prepare the suspension. Materials used include chalk, tragacanth, syrup BP, double strength chloroform water, distilled water, and concentrated cinnamon water.



Before adding all the materials, we were initially triturated chalk and tragacanth using mortar and pestle to assure these two powders mixed evenly.



After trituration, all other materials are added subsequently. The materials are stirred vigorously in the mortar to produce suspension. Distilled water is added up to the volume desired to form the suspension.



5mL of suspension is poured into the small weighing boat from Group 1 to Group 4 (difference in amount of tragacanth added) respectively in order to compare the texture, clarity and colour of suspension among these groups.



50mL of the suspension is poured into the measuring cylinder to observe the sedimentation occur in suspension.



Height of sedimentation is observed and measured using a ruler every 5 minutes. The measurement is taken within one hour.



10mL of the suspension is inserted into a centrifugation tube. Then, the tube containing suspension is then put into the rotofix centrifuge.



This is the list of standard of operation procedure for rotofix centrifuge.



Viscosity of the suspension is measured using the viscometer.











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