USE OF WETTING AGENT IN SUSPENSION

PHARMACEUTICAL PRODUCT DEVELOPMENT

NFNF2213

SEMESTER 1

SESSION 2016/2017

LAB REPORT 1

LECTURER : DR. HALIZA KATAS 

GROUP MEMBERS :

NISHAAL KORAN (A153334)

TAN MIN ANNE (A152663)

MUHAMMAD ROSMAN BIN JUNAIDI (A153262)

MUHAMAD HAZWAN BIN HARUN (A152983)

LEOW PUI MUN (A152593)

Introduction :

The word ‘suspension’ implies a two-phase system which consist of a finely divided solid dispersed in a liquid. Suspensions are heterogeneous systems made up 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 made up of particulate matter which is essentially insoluble in, but dispersed throughout the continuous phase. Suspensions are often prepared for oral administration as sweetened and as non-sweetened for many parenteral routes of administration.

Suspensions have their advantages over other dosage forms. Drugs in suspension are chemically more stable than in solution. However, suspensions possess certain disadvantages as well such as physical instability. Physical instability whereby they tend to settle over time causing lack of uniformity of dose. This can be reduced by precise formulation and by shaking the suspension before each dose is administered. In short, trying to eliminate separation is not the best option but to minimize the rate of settling and to allow re-suspension. One of the strategy is to use wetting agent like tragacanth to reduce surface tension.

Objective :

The objective of the investigation is to study the effect of different amount of tragacanth on the sedimentation rates of suspensions.

Materials :

Chalk

Tragacanth

Concentrated peppermint water

Double strength chloroform water

Distilled water

Syrup BP

Apparatus :

1 ml graduated pipette

Pipette bulb

Weighing boat

Set of mortar and pestle

200 ml graduated cylinder

100 ml beaker

Parafilm

Weighing balance

Viscometer

Plastic bottle

Dropper

Methodology :

1. A suspension of Pediatric Chalk Mixture (150ml) is prepared according to the following formula :

Ingredient	Suspension
	A	B	C	E
Chalk (g)
Tragacanth (g)
Concentrated peppermint water (ml)
Syrup BP (ml)
Double Strength Chloroform water (ml)
Distilled water q.s. (ml)

2. 5 ml of the suspension of each formulation is poured into a weighing boat and labelled. Each suspension is observed and compared based on the texture, clarity and colour.

3. The sedimentation rate of each suspension is determined. The suspension is shaken vigorously to make sure all the particles are uniformly suspended and the time is noted. The boundary between the sediment and the supernatant is observed and the time taken for the boundary to pass each 10 ml graduation until the volume of sediment reaches 80 ml is recorded.

4. The graduated cylinder is set down on the lab bench, and the lab timer is started at this point.

5. The sedimentation volume of the suspensions A to C is recorded at t = 0, 2, 5, 10, 15, and 30 min.

6. The data obtained is recorded in the following table :

Suspension	Sedimentation volume at pre-determined time (min)						Distinct boundary (yes/no)
	0	2	5	10	15	30
A
B
C
E

7. The sedimentation volume ratio is calculated using the following formula :

            Sedimentation volume ratio = Hu/Ho

                Hu : ultimate height of the sediment

                Ho : initial height of the total suspension

8. The ease of re-dispersibility of each formulation is examined after the last measurement. This is done :

    i) The Parafil is snugged on the mouth of the graduated cylinder and the seal is re-enforced with             our hand.

    ii) The number of inversions it takes to completely re-disperse the drug is counted.

   iii) The observation is recorded.

9. 95 ml of suspension is poured into a 100 ml beaker and the viscosity of the the suspension is determined using viscometer at 100 rpm for 30 seconds.

10. The data is recorded in the following table :

Suspension	A	B	C	E
Viscosity(cP)
Mean
SD

11. Each suspension is poured into a plastic bottle. All the suspension is stored for 4 days then, the ease of redispersion in each system is determined as well as the most acceptable system.

Results :

Suspension	Sedimentation volume at pre-determined time (mL)						Distinct Boundary
	0	2	5	10	15	30
A	0	0	30	20	18	18	Yes
B	0	0	0	15	20	18	No
C	0	0	0	2	18	20	No
E	0	0	0	0	0	0	No

 Discussion :

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

Suspension	Amount of tragacanth(g)	Texture	Clarity and Appearance	Colour
A	0.0	Water-like, least viscous, fastest to sediment	Least cloudy, 2 distinct layer after sedimentation	Less milky
B	0.1	Viscous, slower to sediment	Cloudy	Milky white
C	0.3	More viscous, slowest to sediment	Cloudy	Milky white
E	0.5	Most viscous, no sedimentation	Opaque	Yellowish-white

     

       Based on the observation, we can see that suspension A has the least viscosity. Suspension C is more viscous than suspension B. However, suspension E is the most viscous.

       In suspension A,  the wetting agent tragacanth powder is not present , causing the suspension to sediment very quickly as well as behave as water-like and can flow freely. Therefore, it has the least viscosity. Suspension B is less viscous then suspension C as it has lesser wetting agent tracaganth powder. Therefore, the chalk will sediment quickly in suspension B compare to suspension C. Suspension E serves as a control as it does not contain any chalk. The amount of wetting agent will influence the sedimentation rate as wetting agent lowers the surface tension and the contact angle of chalk and liquid particles.

2.      2.Plot H_u/ H_o vs time for each suspensions. (Table 1) Discuss the findings .

Sedimentation volume ratio = Hu/Ho

Hu: ultimate height of the sediment, i.e., the height of the sediment at a particular time

Ho: initial height of the total suspension

Hu/Ho value of Suspension	0	2	5	10	15	30
A	0	0	0.2	0.13	0.12	0.12
B	0	0	0	0.1	0.13	0.12
C	0	0	0	0.01	0.12	0.13
E	0	0	0	0	0	0

Based on the graph constructed, suspension A which does not contain tragacanth wetting agent shows a high sedimentation volume ratio. At the first 5 minutes, the sedimentation height increases dramatically. However, the value drops to 0.13 and remained constant after that. At the beginning, the chalk particles sediment very quickly due to the absence of tragacanth wetting agent, thus proving the sedimentation ratio at the first 5 minutes. Later on, the sedimentation ratio decreases until a constant value because the chalk particles compressed each other, flocculation occurred, which causes the sedimentation value to decrease.

For suspension B and C which contain the tragacanth wetting agent , the sedimentation ratio is lower than A . Tragacanth helped to lower the interfacial tension and contact angle between chalk particle and liquid particles. The ratio will remain constant after a certain time because the sedimentation volume had reach the limit. Suspension B has a higher sedimentation ratio because it has lesser tragacanth wetting agent, thus allowing chalk powder to sediment more quickly.

 3. Briefly explain the principle of analysis using viscometer. Plot the viscosity vs tragacanth content. Discuss the findings.

Suspension		A			B			C			E
Viscosity (cP)	1.38	1.62	0.87	1.86	2.28	2.04	2.76	2.16	2.40	0.54	0.48	0.57
Mean		1.29			2.06			2.44			0.53
Standard Deviation		0.31			0.17			0.25			0.04

Amount of tragacanth (g)	0	0.1	0.3	0.5
Viscosity (cP)	1.29 ± 0.31	2.06 ± 0.17	2.44 ± 0.25	0.53 ± 0.04

There are many ways to measure viscocity of liquid. One of the way is by using viscometer. In this experiment, the viscocity of the suspension is measured by using rotational viscometer. The rotational viscometer basically consists of two parts which is a head unit with a motor and a spindle that is driven by the motor. The viscosity is determined by measuring the resistance of a spindle rotating in the sample. When immersed in a sample fluid, the rotational viscometer senses torque (twisting force) required to rotate a spindle at constant speed to calculate the viscosity of the fluid. The measured torque is proportional to the dynamic viscosity. The torque required to maintain constant rotational rate while overcoming viscous resistance and it is correlated with viscosity. Thus, it can be said that the dynamic viscosity is proportional to the measured torque. The continuous changes in magnetic field cause the rotor magnet to spin. There are different types of the spindle that are used in the rotational viscometer. For us, we are using the thinner spindle as we are measured the suspension in the small beaker.

In the making of suspension, we must put a suspending agent. This experiment we are using tragacanth as a suspending agent. The function of suspending agent is to help the suspending medium to support the insoluble solid and thus decrease the rate of sedimentation. It will suspend the chalk in the external phase.

             We are using 4 formulations in this experiment which is sample A, B, C and E. All the formulations contain different amount of tragacanth in gram. Theoretically, the more amount of tragacanth used, the more viscocity of the suspension. Tragacanth will lower the interfacial tension and thus, increase the viscosity of the suspension

            From the graph plotted based on the result obtained from the experiment, we can see that the viscocity of the suspension increases gradually with the increase amount of the tragacanth and suddenly the viscocity is drop at the end. This is because for the sample E, there is no active ingredient which is chalk. Eventhough the amount of tragacanth is higher in the sample E, it cannot make the suspension become viscous as there is no activity of lowering interfacial tension of chalk by tragacanth. Sample C with 0.3 g of Tragacanth is the most viscous suspension in this experiment with an average viscosity of 2.44 cP. The least viscous suspension among the sample that have active ingredient is Sample A which has 0.1 g of Tragacanth record an average viscosity of 1.29 cP. Sample E is the least among others with an average viscocity of 0.53 cP.

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

After we stored the suspensions for 4 days, the ease of redispersion of each suspensions are as follows :

Suspension	Ease of redispersion of each suspensions
A	Normal
B	Easy
C	Very Easy
E	Difficult

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

Based on all the observations, we found that the most acceptable product are product of Sample C. This is because Sample C have the precise amount of Tragacanth powder in the suspension. The suspension with too many Tragacanth are too viscous and have smooth texture while suspension with no or too small amount of Tragacanth(sample A and B) have less smooth texture with intermediate of redispersion rate of the suspension if we compare to sample C.

As the amount of Tragacanth used increase, the suspension will become more viscous and stable against coagulation. Tragacanth may increase the viscosity of the aqueous vehicle and thus slow the rate of sedimentation of the particles but they will also form adsorbed layers around the particle so that the approach of their surfaces and aggregation to the coagulated state is hindered. Viscosity are important for acceptable suspension but the suspension must be in the normal viscocity in which the viscocity of the suspension is not too high and not too low. When the suspension is too viscous it will cause difficulty in administration of product by patient.

Ease of redispersion of the sediments in the suspension are vital for uniformity of dose. It is to prevent from the suspension having inaccurate dosing which can be overdose or underdose. By having a good suspension which is readily to be redispersed, the accurate dose most probably can be achieved. From all the sample, Sample C is the sample that can easily redisperse. Tragacanth will support the insoluble solid in the suspending medium for a longer time to prevent it from forming hard cake that is difficult to be redispersed. Flocculation is the way to prevent formation of hard cake. Tragacanth also can bother the sedimentation rate of suspension. When the amount of tragacanth powder increase, sedimentation rate will occur more slowly and thus sediment height will be lower.

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.

Excipient	Function
Tragacanth	Wetting agent, to increase the viscosity of solution, to slow down sedimentation of particles in suspension
Concentrated Peppermint Water	Acts as flavouring agent
Syrup	Acts as flavouring agent
Double Strength Chlorofoam Water	Acts as preservative agent to reduce microbial growth in the suspension
Distilled Water	Acts as a solvent

Chalk powder is an active ingredient in the suspension. The general use of chalk powder is to treat diarrhea as it adsorb excess fluid in the faeces.

Tragacanth powder acts as wetting agent so that the stability and uniformity of a solution is ensured whereby there are no two distinct layers of ingredients present in the suspension. Therefore, the amount of tragancath will determine the viscosity of solution, texture and appearance. When the tragacanth is present in the solution, the solution looks more cloudy and smooth. However, the amount of tragacanth in the suspension must be not be too much. The more the amount of tragacanth used, the slower the sedimentation occur. If the viscosity of suspension is too high, it might results in caking and difficult to pour which will be inconvenient for the patient.

Conclusion :

The rate of sedimentation and height of sediment formed in the suspension depend on the different amount of Tragacanth powder used during the formation of suspension. The higher the amount of Tragacanth powder, the lower the height of sediment formed. This happens due to the action of Tragacanth powder that prevent the solution from forming sediment.