Experiment 3 ointment

NFNF2263

PHARMACEUTICAL TECHNOLOGY 2

SEMESTER 2

SESSION 2012 / 2013

PRACTICAL REPORT 3

TITLE : EXP 3: Evaluation of different effects of ingredients towards the ointment formulation.

NAME        :                     1. LIM ANNE YEE (A131494)
                                             2. LIM GUCCI (A136085)
                                            3.LIM ZEN HUEI (A136194)
                                            4.TEH THIAN SIANG (A136169)
                 5. PUTERI EFFY NASTASHEA BINTI HOSLAM (A136042)

LETURER                     : DR HALIZA BINTI KATAS

FACULTY OF PHARMACY

UNIVERSITI KEBANGSAAN MALAYSIA

Title:

Evaluation of different effects of ingredients towards the ointment formulation.

Objective:

To study the effect of ointment composition towards the physical properties of the ointment and the rate of drugs release from the ointment formulation.

Introduction:

Ointment formulation is a suitable semisolid dosage form for the application on the skin. It is an oily preparation that contains one or more of the dissolved active drug or distributed homogenously. A good ointment should have attractive texture, easily applied onto the skin and release the active drug readily.

Usually, ointment consists of active ingredients (powder or liquid) which are incorporated into the oily semisolid carrier. In the pharmaceutical industry, the ointment preparation is used for topical treatment at the application site and to increase the moistures of the skin (emollient effects).

Apparatus:                                                                 Ingredients:

Weighing instrument                                       Emulsifying wax

Weighing boat                                                 White soft paraffin

100ml beaker                                                   Liquid paraffin

Heater                                                             Acetylsalicylic acid

1 set of cream and spatula                                          Distilled water

Mortar and pestle

Dialysis bag (10cm)

Thread

Glass rod

Water-bath

1 set of pipette (5 ml) and pipette-bulb

1 plastic kuvet

Spectrophotometer UV/Vis

Procedure:

1.      50g of Emulsifying Ointment was prepared for the following formulation:

Emulsifying Ointment	Ingredients (g)			Total (g)
	Emulsifying wax	White soft paraffin	Liquid paraffin
I	21	25	4	50
II	17	25	8	50
III	13	25	12	50
IV	9	25	16	50

1. 5 g of cream was taken and put into the weighing boat and was labeled. The texture, clarity and the color of the cream was described and compared.
2. 1.5 g of Acetylsalicylic acid powder was incorporated into 30 g of cream which was prepared by levigation technique.
3. Acetylsalicylic acid was filled into the dialysis bag and the two side of the bag was tied.
4. The bag was put into a beaker (200ml) filled with distilled water (100ml) which was heated to 37°C.
5. Every 5 minutes, one aliquot sample (3 – 4 ml) was pipette and the release of Acetylsalicylic acid from the cream base was determined by using spectrometer UV-visible. The distilled water was stirred with glass rod before the sample was taken.

Results  :

Time(min)	UV absorption at 310 nm
0	0
5	0.036
10	0.040
15	0.065
20	0.082
25	0.109
30	0.122
35	0.141
40	0.177
45	0.180
50	0.225
55	0.246
60	0.250

Discussions:

1.      Compare the physical characteristics of the ointments and explain.

Group	Material (g)				Texture of ointment			Clarity	Colour
	Emulsifying wax	White soft paraffin	Liquid paraffin	Spreadibility		Greasiness	Hardness
5	21	25	4	Most difficult		Least greasy	Hardest	Turbid	White
6	17	25	8	Difficult		Relatively greasy	Hard	Turbid	White
7	13	25	12	Intermediate		Greasy	Soft	Turbid	White
8	9	25	16	Easy		Most greasy	Softest	Turbid	White

The ointments that are formulated by each group are the same in the composition of white soft paraffin however the composition of the emulsifying wax and the liquid paraffin are different for each group. The quantities for both of these materials are varied to make up a total amount of 50g of ointment. All the ointment that is formulated is white in colour and turbid. The degree of the turbidity of the ointment depends on the amount of emulsifying wax added to the formulation. As the amount of the emulsifying wax increased in the formulation it will be easier for the ointment to spread upon application. The greasiness of the formulation also increases as the amount of emulsifying wax increases in the formulation. The quantity emulsifying wax in the formulation will also cause the hardness of the ointment to vary. The lower the quantity of emulsifying wax, the softer the ointment produced.

2. Plot a graph of UV absorption versus time. Give reason.

In this experiment , the dialysis bag is resembled to the phospholipid bilayer of the cell membrane of human where the absorption occurs across the membrane into the distilled water which is resembled to the blood plasma. The temperature of distilled water is maintained at 37ºC which is the temperature of human body.

The amount of drug absorbed into the blood circulation is represented by the concentrations of the drug in the distilled water. The UV absorption represents the concentration of the drug that crosses the membrane and reaches into  the distilled water.

In theory, the UV absorption is proportional to the time of the release of salicyclic acid across the membrane to distilled water. The gradient of the graph shows the rate of drug release across the membrane of dialysis bag.

The graph shows that as the time increases, the concentration of the salicyclic acid in the distilled water is increasing. Along the time until a particular point, the gradient of the graph decreases thus the releasing rate is reduced. Along the progression of the experiment, the concentration of salicyclic acid in the dialysis bag and the distilled water become isotonic because the salicyclic acid keeps moving into the distilled water. The gradient of graph decreases because the salicyclic acid diffuses into and out of the membrane of dialysis bag in an equilibrium state. At the late stage, the releasing rate increases. This may be contributed by the experimental error such as leakage of the drug whereby the thread is not tight tightly enough or  the distilled water is stirred too vigorously.

3.      Plot graph UV absorption against time for the ointment formulation with different composition. Compare and discuss the results.

From the graph above, the formulation 1 has the highest concentration of acetylsalicylic acid in the distilled water. Theoretically, low concentration of acetylsalicylic acid in the distilled water should be shown. Physically, formulation 1 ointment is harder than the other ointments. Formulation 1 should show slow release rate due to the high proportion of the emulsifying wax and low proportion of liquid paraffin. Usually hydrophilic acetylsalicylic acid can disperse uniformly in the ointment, due to high proportion of the emulsifying agents (emulsifying wax). However, the oil phase (liquid paraffin and soft paraffin) is not enough for the acetylsalicylic acid to diffuse through the membrane. Hence concentration of acetylsalicylic in the distilled water should be low.

            From the book Differential diagnosis in dermatology written by Richard Ashton, Barbara Leppard, the ideal formulation of ointment has the percentage of emulsifying wax, white soft paraffin and liquid paraffin at 30%, 50%, 20% respectively.

      The graph shown indicates that formulation 2 has higher concentration of acetylsalicylic acid in distilled water than formulation 3. Theoretically, as the amount of emulsifying wax decrease and amount of liquid paraffin increases, the acetylsalicylic acid can diffuse through the membrane better which means that isotonicity can be achieved between ointment and the surrounding distilled water in a faster way. In formulation 2, the percentage of emulsifying wax, white soft paraffin and liquid paraffin should be 34%, 50%, 16% respectively. Meanwhile, in formulation 3, the percentage of emulsifying wax, white soft paraffin and liquid paraffin should be 26%, 50%, 24% respectively. Both formulations shows only 4% difference with the ideal formulation. Thus, these formulations encourage the diffusion of drugs into the distilled water through the membrane.

      Formulation 4 has the lowest concentration of acetylsalicylic acid in distilled water. Although there is a high amount of liquid paraffin to assist in the diffusion of acetylsalicylic acid, but insufficient emulsifying wax causes acetylsalicylic acid unable to disperse properly in ointment. Therefore, acetylsalicylic acid has low concentration in distilled water.

      As the time goes on, the concentration of acetylsalicylic acid in distilled water gradually increases for every formulation. However, in formulation 2 there is a slight decrease in concentration during 30 minutes to 35 minutes. This is due to uneven stirring or absence of stirring before taking out the volume, the concentration of acetylsalicylic acid is unevenly distributed in the distilled water. Hence, the volume taken out maybe less concentrate than the previous concentration.

4.      What is the function of each ingredient using in the preparation of ointment. How the usage of different content of Emulsifying Wax and Liquid Paraffin influence physical characteristic of the ointment formulation and its drug releasing rate?

Emulsifying Wax	Substance added to an emulsion to prevent the coalescence of the globules of the dispersed phase. They are also known as emulgents or emulsifiers. They act by reducing the interfacial tension between the two phases and forming a stable interfacial film. It can increase the water solubility of the ointment.
White Soft Paraffin	It is reserved for products with colourless, white or pale ingredients. It inhibits water loss from the skin by forming a greasy layer, and this in turns improves the hydration of the skin in dry scaly conditions.
Liquid Paraffin	Liquid paraffin increases the lipophilicity of ointment, so that it can penetrate the membrane. It also used to reduce the viscosity of the ointment.
Acetylesalicylic acid	An active ingredient used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication.

Liquid paraffin increases the liphophilicity of ointment, so that it can penetrate the membrane. Emulsifying wax increase the water solubility. The higher the amount of emulsifying wax, the greater the capability of the ointment to hold water. The greater the amount of the liquid paraffin, the higher the lipophilicity, the greater the penetration of the drugs .

Conclusion:

Physical properties of the ointment and the rate of release of drug from the formulation can be influence by different composition of the ointment. Thus, the components of the formulation must be in suitable proportion to produce a drug which has desired therapeutic effect.

References:

1.      Aulton, M.E. 2002. Pharmaceutics: The science of dosage form design. Edinburgh: Churchill Livingstone

2.      Florence,A.T. & Attwood, D. 1998. Physico-chemical principles of pharmacy. 3rd Ed. New York: Macmillan.

Experiment 2 Suspension

FACULTY PHARMACY

PHARMACEUTICAL TECHNOLOGY II

(NFNF 2263)

SEMESTER 2

SESSION 2012/2013

LAB REPORT 2

NAME            :

LIM ANNE YEE (A131494)

LIM GUCCI (A136085)

LIM ZEN HUEI (A136194)

THE THIAN SIANG (A136169)

PUTERI EFFY NASTASHEA BINTI HOSLAM (A136042)

 

LECTURER  : DR. HALIZA BINTI KATAS

DATE             : 18^th MARCH 2013

Title

Assessment of the Effects of Different Compositions of Ingredients Used on the Characteristics of a Suspension Formulation

Introduction

A suspension formulation is a type of disperse system where the insoluble solid particles are dispersed homogenously in the liquid phase. A good suspension must be in a homogenous form after shaking, easily poured from the container, has a uniform solid particle size and possess better feel and taste. Sediment that is formed upon storage has to be easily redispersed after shaking, forming homogenous suspension.

            In general, suspension comprises of an active ingredient (solid phase) in a liquid carrier, a wetting agent, flavouring and colouring agents and preservatives. The function of a wetting agent such as tragacanth is to reduce the interfacial tension between the solid particles and the liquid. Suspension can be classified into a coarse suspension where the diameter of the particles is more than 1 µm or a colloidal suspension where the particle size is less than 1 µm. In pharmaceutical practice, suspension is used to improve the stability of the active ingredient, taste, and bioavailability.

Objective

To study the effects of using different amounts of tragacanth on a suspension formulation

 Apparatus and Material

I. Apparatus

Weighing balance                                            A set of pipette (1ml) and bulb-pipette

1 weighing boat                                              1 centrifugation tube 15ml

A set of mortar and pestle                              1 beaker 100ml

Plastic bottle 150ml                                         Centrifugation equipment

Measuring cylinder 50ml                                 Viscometer                

A measuring cylinder 200ml                          

II. Materials

Chalk                                                               Syrup BP

Tragacanth                                                      Double-strength Chloroform Water

Concentrated Peppermint Water                    Distilled water

 Procedures

1.      A suspension of Paediatric Chalk Mixture (150ml) is prepared using the formulation below:      

Chalk                                                                                       3g Tragacanth                                                                    Refer to table 1 Concentrated Peppermint Water                                           0.6mL Syrup BP                                                                               15mL Double Strength Chloroform Water                                      75mL Distilled Water, q.s.                                                              150mL

Table 1

Paediatric Chalk Mixture	Group	Tragacanth (g)
I	1, 5, 9	0.0
II	2, 6, 10	0.1
III	3, 7, 11	0.3
IV	4, 8, 12	0.5

2.      Some of the suspension formed (5ml) is poured into the weighing boat and labelled. State and compare the texture, clearness and colour of the suspension formed.

3.      50ml of suspension formed is poured into the 50ml measuring cylinder and the height of the solid phase sediment in the cylinder is measured at intervals of 0, 5, 10, 15, 20, 25, 30, 40, 50 and 60 minutes.

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

5.      10ml of suspension is poured into a centrifugation tube and the height of the solid phase formed after centrifugation (1000rpm, 5 minutes, and 25°C) is determined.

RESULTS AND DISCUSSION:

1.      Compare the physical characteristics of the suspensions and give your comment.

Group	Amount of Tragacanth (g)	Texture	Clarity, appearance	Colour of suspension
5	0.0	Less viscous, rough texture and disperse easily	Less cloudy, has 2 layer	Less milky
6	0.1	Viscous	Moderately cloudy	Milky
7	0.3	Viscous	Opaque, cloudy	Milky
8	0.5	More viscous	Opaque, cloudy	Milky

As the amount of tragacanth added to the formulation is increased, the more viscous the suspensions become. Tracaganth acts as a suspending agent in which it provides ‘structure’ to the medium in order to support the suspensoid. More viscous a suspension is, longer time is taken for the suspended particles to sediment and this will allow the pharmaceutical product to be withdrawn from the container to be consumed by the consumer. If the disperse phase will sediment, it will be eeasily redisperse and stay disperse in the medium for a longer time compared to the formulation without tragacanth. As the amount of tragacanth that added to the formulation increases, the more opaque and cloudy the product will be. The opacity and the cloudiness indicates that the disperse particles is totally dispersed in the medium. If no tragacanth is added to the formulation, the product will appear to be separated in two phase in which the supposed to be disperse phase seems to sediment at the bottom of the container.

2.      Plot the graph of height of the solid phase in the measuring cylinder against time. Give your comment.

Time (minute)	0	5	10	15	20	25	30	35	40	45	50	55	60
Height of solid phase (millimetre)	0	1	3	7	11	15	18	20	20	21	21	21	21

The graph above shows the relationship between the heights of sedimentation with time. As observed on the graph, it is shows that the longer time taken the higher the heights of sedimentation. The suspension was white in colour, we need to use some light to observe the sedimentation clearly to avoid from making error. For the last 20 minutes the height of sedimentation of suspension has become no change which is it maintain at 21 mm. This is because all of the Tragacanth that is contain in the suspension already sedimented. 

3.      Plot the graph of height of solid phase against time for different amount of tragacanth in the suspension. Give your comment.

Time (minute)		Height of the sediment (millimetre)
		0	5	10	15	20	25	30	35	40	45	50	55	60
Amount of tragacanth (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
	0.3	0	2	4	6	7	8	9	9	10	10	10	10	10
	0.5	0	1	3	7	11	15	18	20	20	21	21	21	21

The graph above shows the relationship of the height of sedimentation with time for four different suspensions that contain different amounts of tragacanth. The height of sediment decreases as the weight of tragacanth increases. The more the tragacanth content, the less the sediment formed. Suspension which contains more tragacanth is more stable as the tragacanth is the suspending agent. It is added to reduce sedimentation by structuring the continuous phase to produce a deflocculated system. For formulation with optimum amount of tragacanth, the system is stable and no slow flocculation occurs. A good suspension is a suspension that the sedimentation process does not happen quickly when the suspension is shaken. This is to allow that all the material in the suspension can disperse for a longer time to increase the efficiency of suspension administration.

However from the graph, it shows that the more the tragacanth content, the more the sediment formed. This may due to the experimental error. In the suspension which is containing 0.0g of tragacanth, the absence of tragacanth results in quick sedimentation of solid particles and hence a flocculated system is produced. For the suspension which is containing 0.5 g amount of tragacanth, the sedimentation gradually formed with a increase of height (21mm).

4.Explain briefly the mechanism of viscometer analysis. Plot a graph of viscosity of the suspension versus the amount of tragacanth (g). Give explanation.

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

 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

        Rotational viscometers use 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. It is operates as the motor of viscometer rotate with the speed 300rpm. Stirrer is rotated by disc which in turn moved by spring more than 180°.LED emit infra red radiation and diffuse through the disc and then detected by a photo diod. The infra red radiation detected and read by the photo diod is depend on the change of degree of disc rotation.

. According to theory, viscosity decreases from suspension IV to suspension I. The graph obtained should be linear where the viscosity of suspension is directly proportional to the amount of tragacanth.From the graph above, Suspension IV is the most viscous suspension compared to other suspensions formed. The more tragacanth added, the more viscous of the suspension being formed.. Chalk is suspended by tragacanth in the liquid phase and form suspension. When the amount of tragacanth is increased, suspension that forms will be more viscous.

 However, we do not obtain such graph because there are some mistakes in this experiment. For the 0.1 g of tragacanth in suspension should be more viscous than 0.0g of tragacanth in suspension. This may be due to we add insufficient amount of powder when we making of suspension or viscometer did not dipped well into the suspension when it is operated.Besides, insufficient cleaning of the disc will affect the viscosity detected.

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

Tragacanth(g)	0	0.1	0.3	0.5
Height Ratio (x ±SD)	7	11	17	20

From the graph, the height ratio is increased as the volume of tragacanth increased. This result is not correct due to experiment error. The error maybe due to incorrect handling of the experiment procedure .The actual result should be decreased of height ratio when the volume of tragacanth increased. This is because due to the ability of the tragacanth acts as a suspending agent and can hold the heavy and insoluble powders in the suspension. Thus, increase volume of tracaganth powder, less chalk powder will be sediment on the bottom of the tubes and separation of the suspension will be lesser. Since the suspension produces sediment on storage it must be readily dispersible so as to ensure the uniformity of the dose. If sediment remains even after shaking vigorously for specified time, the system is described as caked. All the suspensions were found to be redispersible irrespective of their concentration.

6. What is the function of each ingredient used in the suspension preparation? How does the different amount of Tragacanth powder affect the physical characteristics and stability of the suspension formulation?

Chalk	Active ingredient which acts as absorbent and used to treat diarrhea.
Tragacanth powder	Suspending agent and wetting agent that used to decrease interfacial tension between solid particle and liquid from continuous phase.
Concentrated peppermint water	Flavouring agent in suspension.
Syrup BP	Viscosity thickener of suspension. Sweetening agent.
Double strength chloroform water	Flavouring agent, preservative, and solvent.
Distilled water	Diluent in suspension.

        As amount of tragacanth powder added increases, suspension will be smooth, cloudy and stable. In a more stable suspension, sedimentation is difficult to occur or takes a longer time to develop. With higher content of tragacanth powder in suspension, there is less flocculation, but once the sedimentation occurs after a period of time, redispersibility of suspension becomes more difficult.

        For suspension with lesser amount of tragacanth powder, it will be less smooth, less stable and clearer. Sedimentation occurs more easily but redispersibility is easier compared to suspension with high content of tragacanth powder.

Conclusion:

Different amount of Tragacanth powder will affect the rate of sedimentation, the height of sediment formed and viscosity of suspension.

Reference:

1. Ghosal & Srivastava, 2009. Fundamentals Of Bio analytical Techniques And Instrumentation. PHI Learning Pvt. Ltd.

2. John F. Marriott, Pharmaceutical Compounding And Dispensing, 2006, Pharmaceutical Press Sdn Bhd

3. http://priory.com/pharmacy/Suspension_Gum_SuspendingAgent.htm