EXPERIMENT 1 : THE USE OF WETTING AGENT IN SUSPENSION

INTRODUCTION:

Suspension can be divided into oral, topical, parenteral and ophthalmic. It is a formulation whereby the insoluble solid is being suspended in a liquid by the aid of suspending agent. The term “suspension” refers to a two-phase system consisting of a finely divided solid dispersed (suspended) in a liquid (the dispersing medium). Generally, suspensions are heterogeneous systems consisting of at least two phases. The dispersed or internal phase is made up of particulate matter which is essentially insoluble in, but dispersed throughout, the continuous phase while the continuous or external phase that is generally a liquid or a semi-solid.

Suspensions possess certain advantages over other dosage forms. Some drugs are insoluble in all acceptable media and must, therefore, be administered as a tablet, capsule, or as a suspension. Moreover, some drugs are chemically stable in the form of suspension rather than in solution. One of the function of suspension is to mask the bad taste of some drug. Suspensions are intended for oral administration as sweetened, flavored formulations or for topical application where they are referred to as "lotions." In some cases, suspensions are also used as non-sweetened, non-flavored formulations for many parenteral routes of administration (e.g., intraocular, intranasal, IV, IM, ID, SC). 

However, suspensions also possess some disadvantages relative to other dosage forms. The primary disadvantage is their physical instability. For example, they tend to settle over time leading to a lack of uniformity of dose. This can, however, be minimized by careful formulation and by shaking the suspension before each dose is delivered. Therefore, the best strategy is not to try to eliminate separation, but rather to decrease the rate of settling and to permit easy re-suspension of any settled particulate matter. Thus, wetting agents which is also known as surfactants have to be added because the drugs are not readily suspended in the liquid medium which is the aqueous phase. The examples of wetting agent are tragacanth which is used in this experiment. The role of surfactant is to reduce the interfacial surface tension between the drug particles and the suspension vehicles.

In short, a good suspension should be physically and chemically stable, resistant to microbial contamination, homogenously dispersed when shaken, easily poured and is consist of uniform dispersed size particles. Besides, suspension should be able to disperse when the solid particles settled. These properties are being investigated in this experiment. For example, the physical appearance of the suspension is being studied by observation while the viscosity and rate of sedimentation is being studied using the viscometer and centrifuge.

AIM: 

To find the effect of different amount of tragacanth on the sedimentation rates of suspensions.

PROCEDURES:

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

INGREDIENTS	SUSPENSION
	A	B	C	E
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 Choloroform water (mL)	75	75	75	75
Distilled water q.s (mL)	150	150	150	150

2.      5 mL of the suspension was poured into a weighing boat and was labelled each formulation. 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 making sure all the particles were uniformly suspended, and the time was noted. The boundary between the sediment and the supernatant was observed and the time taken for the boundary to pass each 10 mL graduation was recorded until the volume of sediment had reached 80 mL.

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

5.      The sedimentation volume of the suspensions were recorded at t=0, 2, 5, 10, 15 and 30 minutes.

6.      The ease of dispersibility of each formulation was examined after the last measurement by counting the number of inversions taken to compeletely re-disperse the drug.

7.      95 mL of the suspension was poured into a 100mL beaker and the viscosity of the suspension was determined using viscometer at 100 rpm for 30s.

8.      The data was recorded.

9.      Each suspension was poured into a plastic bottle to be stored for a period of 4 days to determine the ease of redispersion in each system.

10.  The most acceptable system was determined.

OBSERVATION: 

Suspension	Tragacanth Used	Observations
		Texture	Clarity	Color
A	0.0	Watery. Less viscous.	The suspension is clear on top but with sediment formed at the bottom.	Transparent on top with white sediment formed at the bottom.
B	0.1	Slightly watery. Less viscous than suspension C but more viscous that suspension A.	The suspension is clear on top but with sediment formed at the bottom. The sediment formed is more compared to suspension A.	Transparent on top with white sediment formed at the bottom.
C	0.3	More viscous than suspension B.	The suspension is opaque and formed a heterogeneous mixture.	The suspension is cloudy white without clear distinct boundary.
D	0.5	More viscous than suspension D. Smooth texture.	The suspension is a clear mixture.	The suspension is clear enough to enable light to pass through it.

RESULT:

Table of time taken for boundary between the sediment and the supernatant to pass each 10ml graduation until the volume of sediment has reached 75ml.

Suspension	Time taken for boundary to pass each 10ml graduation (ml)
	145	135	125	115	105	95	85	75
A	0	20s	36s	50s	1min3s	1min15s	1min25s	1min33s
B	0	32s	54s	1min10s	1min24s	1min38s	1min52s	2min8s
C	0	-	-	-	-	-	-	-
D	0	-	-	-	-	-	-	-

Suspension	Sedimentation volume at pre-determined time (min)						Distinct boundary(Yes/No)
	0	2	5	10	15	30
A	145	34	26	20	18	14	Yes
B	145	82	54	35	28	24	Yes
C	145	37	34	30	30	30	No
D	145	-	-	-	-	-	No

Suspension	Sedimentation volume ratio Hu/Ho at pre-determined time (min)
	0	2	5	10	15	30
A	1	0.23	0.18	0.14	0.12	0.10
B	1	0.57	0.37	0.24	0.19	0.17
C	1	0.26	0.23	0.21	0.21	0.21
D	1	-	-	-	-	-

 Table: Sedimentation volume ratio versus time

Suspension	A			B			C			D
Tragacanth content(g)	0.0			0.1			0.3			0.5
Viscosity(cP)	1st	2nd	3rd	1st	2nd	3rd	1st	2nd	3rd	1st	2nd	3rd
	0.24	0.26	0.23	0.27	0.36	0.33	0.46	0.52	0.48	0.52	0.51	0.56
Mean	0.24			0.32			0.49			0.53
SD	0.016			0.046			0.031			0.026

FORMULA USED:

1. Mean

2. Standard Deviation

DISCUSSION:

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

In suspension A, the texture is watery and less viscous. The suspension is clear on top with white sediment formed at the bottom. The suspension is easily separated as the suspending agent is absent. Suspension B has slightly watery texture. It is less viscous than suspension C but more viscous that suspension A. There is white sediment at the bottom of the suspension while the upper part is transparent. A slightly transparent white suspension is formed after shaking but the sediment started to form again if the suspension is let to be settled overtime.

As for suspension C, it is more viscous than suspension B with smooth texture. The suspension is cloudy white without clear distinct boundary. This shows that heterogeneous mixture is formed. Lastly for suspension D, there no drug (chalk) in it. It shows the highest viscosity among the suspensions prepared. However, suspension D is a clear mixture that it enable the light to pass through it.

Based on the observation, the physical appearances of suspension of the formulations prepared are compared by varying the amount of wetting agent added to them. In this experiment, tragacanth powder is used as the suspending and wetting agent that will decrease interfacial tension between solid particle and liquid from continuous phase. According to Stokes Law, the higher the viscosity of the liquid vehicle, the slower the rate of formation of sediments in the mixture (suspension). Thus, tragacanth which act as the suspending agent helps to reduce the sedimentation rate of particles in suspension in order to prevent caking at the bottom. In fact, it also facilitates redistribution of a suspension upon shaking. On top of that, tragacanth also provide viscosity to the suspension. It is of great importance for stability and pourability of suspensions. For instance, the drug particles settling velocity decreases as the viscosity of the dispersion medium increases, thus they remained dispersed for longer time resulting in higher stability and increase in dosing accuracy.

In this experiment the amount of tragacanth added to the formulation increases from suspension A to C. The higher the amount of tragacanth, the more viscous the suspensions will be. Besides, a more opaque and cloudy formulation will be produced. The opacity and the cloudiness indicates that the disperse particles is totally dispersed in the medium. This is mainly due to the suspension stays disperse for a longer time in the formulation with higher amount of tragacanth compared to the formulation with lesser amount of tragacanth. If tragacanth is absent in the formulation, the product will appear to be separated in two phase at which the disperse phase will sediment at the bottom of the container.

However, the viscosity of suspension should be maintained within optimum range by adding a suitable amount of suspending agent. This is done to yield a stable and compliance pharmaceutical product by ensuring even distribution and allow the pharmaceutical product to be easily withdrawn from the container to be consumed by the consumer. 



2.  Graph of sedimentation volume ratio Hu/Ho versus time 

According to the graph of sedimentation volume ratio versus time ,the sedimentation volume ratio for measuring cylinder A,B and C decreases with time. In this case, adding of suspending agent which is the tragacanth powder will increase the viscosity of the suspension thus decreases the rate of sedimentation .In this experiment, the concentration of suspending agent increases from measuring cylinder A, B and C respectively .The suspending agent in measuring cylinder C had achieve an optimum value, thus, the graph shows a stable ratio of sedimentation volume ratio after 10 minutes. 

3.  

A viscometer is an instrument used to measure the viscosity of a fluid under one flow condition. In general, either the fluid remains stationary and an object moves through it, or the object is stationary and the fluid moves past it. The drag caused by relative motion of the fluid and a surface is a measure of the viscosity. The viscometer used during this experiment is rotational viscometer. It uses the idea that the torque required to turn an object in a fluid is a function of the viscosity of that fluid. They measure the torque required to rotate a disk or bob in a fluid at a known speed. Digital encoder rotational viscometer uses a precision servo motor to drive the shaft. The Spindle or rotor is attached directly to the shaft. High speed microprocessors measure the speed from a digital encoder and calculate the current required to drive the rotor at the test speed. The current required is proportional to the viscosity of the sample under test.

Stoke's law:

As we can see from Stoke’s Law, if we apply flocculation as a means of preventing caking, then we will increase the particle diameter, and thus increase the rate of sedimentation. Now we need some means to reduce this rate of settling, so that the suspension can be accurately dosed before it begins to settle. Practically speaking, the viscosity of the dispersion medium is the only other Stoke’s variable affecting sedimentation rate over which the pharmacist can exert any control. Suspending agents, in this case tragacanth is added to suspensions to thicken the suspending medium, making it more viscous thereby reducing the movement (sedimentation) of suspended particles and physically stabilizing the product.

According to the graph above, the viscosity of the suspension increases when the amount of suspending agent, tragacanth added is increased. Thus, we can conclude that the sedimentation process occurs slower when more tragacanth is added into the suspension, making it more physically stable starting from suspension A, B, C and finally D.

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

Suspension D has the fastest ease of redispersion followed by suspension C and then by suspension B. Suspension A has the slowest ease of redispersion.

Suspension A redispersed the slowest as it does not contain any tragacanth. 

Suspension B and C has the faster ease of redispersion compared to suspension A because there are small amount of tragacanth present in both suspension, which are 0.1 g and 0.3 g respectively. 

Suspension D redispersed the fastest because it contains the largest amount of the tragacanth compared to other suspensions prepared. 

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

            Suspension C would be considered to be most acceptable. It is because suspension C has the most amount of tragacanth. Suspension C is cloudy white with no distinct boundary which indicates that it has the highest stability. It also has the fastest ease of redispersion after the suspensions are stored for 4 days. Suspension D is not considered because it does not contain any active ingredient (chalk).

5. 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.

           Chalk is the active ingredient and tragacanth is the suspending agent. Syrup BP is used as a sweetening agent. Concentrated peppermint water acts as a flavouring which masks the unpleasant taste of the drug to make the drug more platable. Double strength chloroform water acts as an antimicrobial preservative and also adds sweetness to the suspension. Distilled water acts as a vehicle or continuous phase for suspension.

The higher the amount of tragacanth, the more viscous the suspensions will be. Besides, a more opaque and cloudy formulation will be produced. The opacity and the cloudiness indicates that the disperse particles is totally dispersed in the medium. This is mainly due to the suspension stays disperse for a longer time in the formulation with higher amount of tragacanth compared to the formulation with lesser amount of tragacanth. If tragacanth is absent in the formulation, the product will appear to be separated in two phase at which the disperse phase will sediment at the bottom of the container. Therefore it can be concluded that, the higher amount of tragacanth will contribute to a higher stability of the suspension.