LAB DPP1 B6

LAB DPP1 B6

Saturday 15 October 2016

PRACTICAL 1 : THE USE OF WETTING AGENT IN SUSPENSION

TITTLE : The Use of Wetting Agent In Suspension

OBJECTIVE : To investigate the effect of different amount of tragacanth on the sedimentation rate of the suspensions

INTRODUCTION:

          Suspension is a heterogeneous mixture in which the solute particles do not dissolve but get suspended throughout the bulk of the medium. It consists of at least two phases; the continuous or external phase is generally a liquid or a semi-solid and the dispersed or internal phase is solid that generally insoluble in the continuous phase. The internal phase (solid) is dispersed throughout the external phase (fluid) through mechanical agitation, with the use of certain excipients or suspending agents. Unlike colloids, suspensions will eventually settle.

           Suspension can be found in several uses. It can be used for oral administration in the form of sweetened, flavoured formulations and also topical application as what we referred as lotion. Suspensions can also be intended for parenteral administration as non- sweetened, non- flavoured formulations.

          Suspension has its own pros and cons. One of the advantage of suspension is suspension is the only choice if the drug is not soluble in water and non-aqueous solvent is not acceptable, for example corticosteroids suspension. Besides, suspension is most suitable for drugs having unpleasant taste and odour. Moreover, Drug in suspension exhibits a higher rate of bioavailability compared to the same drug of equivalent dose formulated in tablets or capsules. This is due to larger surface area and high dissolution of suspension, for example antacid suspension.

        Meanwhile, the disadvantage of the suspension is it is physically unstable, in other words they tend to settle after a period of time without agitation. This may lead to lack of uniformity of the drug and affect the therapeutic effect. However this can be overcome by shaking the suspension before each dose is delivered so that the solute is fully redispersed. To improve this condition, we should try to reduce the rate of settling and permit easy redispersion. These can be achieved by using wetting agent such as tragacanth to minimize the surface tension.

APPARATUS
1 mL graduated pipette
Pipette bulb
Weighing boat
Mortar and pestle
50 mL graduated cylinder
200 mL graduated cylinder
100 mL beaker
Parafilm ®
Weighing balance
Viscometer

MATERIALS
Chalk
Tragacanth
Concentrated peppermint water (or any flavouring agent )
Double strength chloroform water
Distilled water
Syrup BP

PROCEDURE
1.    A suspension of Pediatric Chalk Mixture (150 mL) was prepared according to the following formula:

Ingredient
Suspension
A
B
C
D
Chalk (g)
3
3
3
-
Tragacanth (g)
0.0
0.1
0.3
0.5
Concentrated peppermint water (mL)
0.6
0.6
0.6
0.6
Syrup BP (mL)
15
15
15
15
Double strength chloroform water (mL)
75
75
75
75
Distilled water q.s. (mL)
150
150
150
150
2.     
5mL of the suspension was poured into a weighing boat and each formulation was labelled. The texture, clarity and colour of each suspension was observed and compared.
3.      The sedimentation rate of each suspension was determined. The suspension was shaken vigorously to make sure all of the particles were uniformly suspended, and the time was noted. The boundary between the sediment and supernatant was observed and the time taken for the boundary to pass each 10 mL graduation until the volume of the sediment had reached 80 mL was recorded.
4.      The graduated cylinder was set down on the lab bench, and the lab timer was started at this point.
5.      For suspension A to C, the sedimentation volume of the suspensions at t = 0, 2, 5, 10, 15 and 30 minutes were recorded.
6.      The sedimentation volume ratio was calculated using the following formula:
7.      The ease of re- dispersibility of each formulation were examined by :
i)                    The Parafilm ® was snugged on the mouth of the graduated cylinder and the seal was re-enforce with gloved hand.
ii)                  The number of inversions it took to completely re-disperse the drug was recorded.
iii)                The observations were recorded.
8.      95 mL of the suspension was poured into a 100 mL beaker and the viscosity of the suspension was determined using viscometer at 12000 rpm for 2 minutes. Data was recorded.






9.      Each suspension was poured into a plastic bottle. After storing all the suspensions for a period of 4 days, the ease of redispersion in each system and which system was most acceptable was determined.
During Lab Session

After 4 Days

RESULT :


AFTER 4DAYS

  Suspension
Amount of Chalk (g)
Amount of Tragacanth (g)
Texture
Clarity
Colour
A
3
0.0
Less Viscous
Cloudy
White
B
3
0.1
Moderately Viscous
Cloudy
Milky White
C
3
0.3
More Viscous
Cloudy
Milky White
D
0
0.5
Less Viscous
Opaque
Yellowish


Height of boundary (mL)
Time Taken (min)
A
B
C
D
150
0
0
0
-
140
0.47
1.12
1.90
-
130
0.70
2.25
2.32
-
120
0.95
2.55
2.95
-
110
1.33
2.72
3.22
-
100
1.71
3.02
3.47
-
90
2.00
3.38
3.82
-
80
2.42
3.70
4.13
-

Table 1
Suspension
Sedimentation volume at pre-determined time (min)
Distinct boundary (yes/no)
0
2
5
10
15
30
A
150
90
34
26
22
18
yes
B
150
135
24
22
20
19
yes
C
150
138
66
22
22
22
no
D
150
-
-
-
-
-
no


Sedimentation Volume ratio of Suspension A:
18/150 = 0.120
Sedimentation volume ratio of Suspension B:
19/150 = 0.127
Sedimentation volume ratio of Suspension C:
22/150 = 0.147

Suspension
Number of Inversions
A
2
B
1
C
1
D
-

Table 2
Suspension
A
B
C
D
Viscosity
First
4.8
5.4
8.4
10.2
Second
4.8
5.1
7.8
9.9
Third
4.8
6.6
7.8
10.2
Mean
4.8
5.7
8.0
10.1
SD
0
0.648
0.283
0.141


Suspension
A
B
C
D
Viscosity
First
4.8
5.4
8.4
10.2
Second
4.8
5.1
7.8
9.9
Third
4.8
6.6
7.8
10.2
Mean
4.8
5.7
8.0
10.1
SD
0
0.648
0.283
0.141

DISCUSSION:
1.      Compare and discuss physical appearances of all the suspensions produced.

Suspension
Amount of Chalk (g)
Amount of Tragacanth (g)
Texture
Clarity
Colour
A
3
0.0
Less Viscous
Cloudy
White
B
3
0.1
Moderately Viscous
Cloudy
Milky White
C
3
0.3
More Viscous
Cloudy
Milky White
D
0
0.5
Most Viscous
Opaque
Yellowish

In this experiment, four suspensions are prepared with varying amount of tragacanth. Suspension A is less viscous due to the absence of tragacanth as wetting agent. Tragacanth gives viscosity to the suspension whereby it is of great importance for stability and pourability of suspensions. The presence of wetting agent facilitates the distribution and dispersion of the lyophobic powders. Absence of the tragacanth as the suspending agent caused the suspensions to sediment very fast and the particles separated into two distinct boundaries. Suspension A looks white and cloudy due to the distribution of the insoluble chalk powders.

Suspension B is moderately viscous due to the presence of small amount of tragacanth. It is cloudy due to the insoluble chalk powder which does not dissolve in the solution. The viscosity contributed by the tragacanth gives the colour of milky white.

Suspension C has greater viscosity compared to B because of the increased amount of tragacanth. The texture is very smooth and cloudy because tragacanth helped to suspend and distribute the insoluble particle evenly. The colour of milky white is due to the viscosity and the chalk powder.

Suspension D is the most viscous because it contains the highest amount of tragacanth. It has the thickest texture causes it to be opaque. Tragacanth dissolves and gives the yellowish colour. Thus, we can say that the viscosity of suspension is depends on the amount of tragacanth.


2.      Plot Hu/Ho vs. time for each of the suspensions (Table 1). Discuss the findings.

Suspension A:
Time (min)
Hu
Ho
Hu/Ho
0
150
150
1.000
2
90
150
0.600
5
34
150
0.227
10
26
150
0.173
15
22
150
0.147
30
18
150
0.120

Suspension B:
Time (min)
Hu
Ho
Hu/Ho
0
150
150
1.000
2
135
150
0.900
5
24
150
0.160
10
22
150
0.147
15
20
150
0.133
30
19
150
0.127

Suspension C:
Time (min)
Hu
Ho
Hu/Ho
0
150
150
1.000
2
138
150
0.920
5
66
150
0.440
10
22
150
0.147
15
22
150
0.147
30
22
150
0.147


            The graph of sedimentation volume ratio against time is plotted. In general, the sedimentation volume ratio decreases as the time increases. The lyophobic chalk powder dispersed evenly in the solution in the beginning. Over a period of time, the insoluble chalk powder sediments to the bottom of the cylinder. The use of tragacanth as wetting agent facilitates the distribution of chalk powder.

            The rate of sedimentation of suspension A is highest because there is no suspending agent to facilitate the dispersion of powder. Absence of suspending agent causes the suspension to become easily separated because it has less viscosity. Thus, the denser dispersed phase sediment in a short time. The sedimentation volume decreases due to gravitational force. Further decrease of the sedimentation volume occurs as the powder settles forming a distinct compact layer. There is a distinct boundary observed due to the absence of suspending agent. This suspension forms a flocculated system. Over time, the floc is pulled downwards and formed sediment.

            Suspension B has a slower sedimentation rate at the beginning. However, the sedimentation rate accelerated after 2 minutes. This may due to error occurred during the compounding procedure. The tragacanth might not be mixed evenly causing the drastic increase of sedimentation rate.

            For suspension C, more amount of tragacanth is available in the suspension. The powder can be well suspended by the tragacanth, therefore the suspending effect is higher than suspension B. Tragacanth is a suspending agent which reduces surface tension and prevent clumping of the dispersed particles. It also increases the viscosity of the solvent and thus suspends the particles preventing it from settle down. The sedimentation rate is the slowest compared to A and B. Slow sedimentation rate indicates suspension C has the highest stability compared to the other. The height of the sediment shows suspension C formed the least compact sediment after 30 minutes. Suspension D does not have sedimentation rate because it does not contain chalk powder. Slow sedimentation rate is preferred as this can ensure the correct dose of active ingredients is delivered.

           

3.      After storing the suspensions for a period of 4 days, determine the ease of redispersion of each.

A is the easiest to redisperse followed by B, C and D. Suspension A is the easiest to be redispersed because it has low viscosity. Weak force applied by shaking can easily redisperse the suspension.

Suspension D is the hardest to redisperse. This is because suspension D has the highest amount of tragacanth making it the most viscous. Viscosity hinders the dispersion of the insoluble particles. The suspension with higher amount of suspending agent takes longer time to be redispersed. High viscosity is not totally beneficial in suspension formulation as when it sediments, it is not easily re-disperse even shaking with strong force. This causes unequal and inaccurate dosing. 

4.      Briefly explain the principle of analysis using viscometer. Plot the viscosity vs tragacanth content (Table 2). Discuss the findings.

There are many types of viscometer for example Gravimetric Capillary viscometer, Stabinger viscometer and  Stabinger viscometer. In this experiment rotational viscometer is used. Rotational viscometers use a motor drive which provide dynamic or shear viscosity results. A rotational viscometer consists of a sample-filled cup and a measuring bob or spindle that is immersed into the sample. The motor turns a measuring bob or spindle in a container filled with sample fluid. While the driving speed is preset, the torque required for turning the measuring bob against the fluid’s viscous forces is measured.





The viscosity of the suspension increases as the tragacanth content increase. Tragacanth is used as wetting agent in which it decreases the surface tension, allow it to spread drops onto a surface and makes the suspension more viscous. It also allows removing of air from the surface and to easy penetration of the vehicle into the pores. Viscosity of suspension is important as it will affect the velocity of sedimentation. From the graph, highest tragacanth content of 0.3g has the highest viscosity of 8.0 cP in which proved that the viscosity of the suspension is directly proportional to the amount of the tragacanth powder in the suspension.


5.      Based on all the observations, which product would be considered to be most acceptable? Explain.

Product/suspension C is the most acceptable because it has the highest amount of tragacanth of 0.3 g which makes it more stable, more viscous and has a smooth and cloudy appearance. Cloudy appearance shows that the white chalk is homogenously and uniformly dispersed in the liquid media. Suspension C settles more slowly and take longer time for sedimentation to occur as the tragacanth keep the finely insoluble materials which is chalk suspended in the liquid by preventing agglomeration and by imparting viscosity. The high viscosity of suspension C also decreases the sedimentation rate. The other suspension with a less amount of tragacanth, have a higher sedimentation rate. The number of inversion of suspension C is only one which indicates it is easily to redisperse back.



6.Briefly explain the function of each excipients used in the suspension formulation. Explain the influence of tragacanth on the physical characteristics and stability of a suspension.


 The concentrated peppermint water and syrup is used as flavoring agents to mask or impart taste of medications. The double strength chloroform water is used for preservatives to avoid microbial growth. Tragacanths is used as wetting agent and influence the physical characteristics of suspension by making it more viscous. Tragacanths act as wetting agents where it forms film around particle and reduce the surface tension. Therefore, the insoluble chalk suspended in the liquid media. The more content of tragacanth, the more uniform the chalk is dispersed in the liquid which make it more viscous. High viscosity prevent sedimentation and thus aggregation or caking in which contribute to the high stability of suspension. Tragacanth also retards crystal growth which makes the formulation stable for a longer period of time.

CONCLUSION
Followed by the result , we can conclude that the trend is less surfactant , easier to redisperse . Viscosity of suspension is important in order to determine sedimentation rate . The suspension easily got separate when we decrease amount of tragacanth (suspending agent) .

REFERENCE

1. Michael E.Aulton, Aulton’s Pharmaceutics The Design And Manufacture of Medicines, third edition, 2007, Churchill Livingstone Elsevier