Different effect of content of material towards the characteristics of ointment formulation

Aim
To study the effect of content of material towards the characteristics of ointment formulation
Introduction 

Ointment are semisolid preparation intended for external applization to the skin or mucous membrane.They are use topically for many purposes such as antiseptic,antipruritis,kerotolytics and astringents.Also some drug absorbed into the general circulation via skin and produce systematic effect.

In the formulation of ointment ,the base forms the main part of ointment/product.An ointment base is of prime importance because it does not only serve as vehicle but also function as the carrier of medicinal agents in the product.It affect overall quality of an ointment,the release rate of drg substances as well as it absorption into the body.

The commonly used  ointment bases are classified into three different group which are oleaginous bases,emulsion bases, and water soluble bases.Drug release rate of percutaneous absorption mainly depend on the nature of the drug itself.However the composition and properties of ointment bases also influences the drug release and percutaneous absorption to the certain extent.Furthermore the different o fdrug incorporation techniques have also been shown to effect the drug release rate.The fastest release rate is obtained with water soluble and emulsion ointment bases and the drug release rate from hydrocarbon ointment bases is usually the slowest. Then,the measurement of release rate can be done via a semi permeable membrane.

Apparatus :                                                        Material :

1) Weighing balance                                        1) Emulsifying wax
2) 1 weighing boat                                           2) White soft paraffin
3)  100 ml beaker                                             3) Acetysalicylic acid
4) slab and spatula                                          4) Distilled water
5) 1 set of mortar and pestle
6) 1 bag of dialysis
7)  thread
8) 1 glass rod
9) 1 set of pipette
10)Spectrophotometer UV      

White Soft Paraffin(Petrolleum jelly)

Liquid Paraffin

Emulsifying Wax

Procedure 

1. The ointment is prepared (50 g) via this formula in 70oC-80oC
     1.1 21 g of emulsifying wax
     1.2 25 g of white soft paraffin
     1.3  4 g of liquid paraffin

2.   The 5 g of ointment is weighed and put in weighing boat,label.

3.   The acetylsalicylic (1.5 g) is mixed with ointment that formed via levigation process.Make sure the powder of acetylsalicylic acid is fine and easily dissolve by using mortar and pestle.

4.    The ointment of acetylsalicylic acid is filled into dialysis bag and tied  both end of bag tightly.

5.    The bag is put into the beaker (100 ml) which consist distilled water (50 ml) which already heated ( in 37oC)

6.    The samples in the beaker contain dialysis bag is pipette (3-4 ml) to determine the release rate of acetylsalicylic acid from ointment by using UV spectrometer.The distilled water must be stir by using glass rod before take for the samples

6. With the interval of each 5 minutes, 3-4mL of the distilled water is pipetted out. The release of acetylsalicylic acid from the ointment is determined by using UV-visible spectrometer. Distilled water is stirred before taking the sample.

Time (min)
	0	5	10	15	20	25
UV absorption at 310nm	0	0.035	0.026	0.009	0.007	0.032

Discussion
1. Compare oinment's physical and give a comment.

Emulsifying ointment	Texture			Clarity	Colour
	Spreadibility	Greasiness	Hardness
I	+	+	++++	Unclear	White
II	++	++	+++	Unclear	White
III	+++	+++	++	Unclear	White
IV	++++	++++	+	Unclear	White

The similarity between of all these emulsifying ointments is unclear and white in colour. Based on the table above, emulsifying ointment IV is the most spreadable and greasy. It is followed by emulsifying ointment III, II and I. Emulsifying wax can give stability to the ointment by binding the water and oil or making them miscible and stable. Hence, higher content of emulsifying wax will cause less spreadibility of the ointment, due to much interaction. Meanwhile, emulsifying ointment I is the most hard compared to the others.

Liquid paraffin contributes to the greasiness and hardness of the ointment. High content of liquid paraffin make the ointment become greasier and decrease in hardness.

2.Plot graph UV absorbance versus time.Discuss

UV absorbance showed the different amount of drugs released from the ointment due to the use of different composition which result in varying absorbance at 310 nm in the first 25 minutes.

3.What is the functions of each substances used as excipients in suspenson formulation ?How different Emulsifying Waxand Liquid Paraffin content can affect the physical and stability of suspension formulation and drug flow rate ?

Emulsifying Wax	emulsifiers	Thickeners in formulation
White Soft Paraffin	Hydrocarbon bases	As vehicle from which drug may be absorbed by the skin Emollient for skin
Liquid Paraffin	Hydrocarbon bases	Reduce viscosity
Acetylsalicyclic acid	Active ingredients	Penerate the follicles and facilitates the removal of ead skin from pores
Distilled water	Diluents	Increase bulk volume

Conclusion:

The balance between the amount of emulsifying wax and liquid paraffin in the ointment is important in achieving the desirable traits without compromising the rate of drug release in order to demonstrate the ideal release of drug in systemic circulation.

References

http://books.google.com.my/books?id=J5vE3Z_ZXJcC&pg=PA86&lpg=PA86&dq=tragacanth+in+suspensions&source=bl&ots=TIoQ-FYlzr&sig=PrXeMxvhKQiPpRvsLcW0m2rhkQU&hl=en&sa=X&ei=1iJeU6n3Cs7k8AWNj4DwCQ&redir_esc=y#v=onepage&q=tragacanth%20in%20suspensions&f=false

Different effect of content of material towards the characteristics of suspension formulation

Objective

To study about the effects when using different tragacanth ingredient on a suspension.

Introduction

    A suspension is a  one type of disperse system that involve a mixture of two substances, one of which is a liquid, while the other is a finely divided solid that dispersed homogenously in the liquid phase. A good suspension must  easily poured from the container,has a uniform solid particle size and possess better texture and the most important is it must be in a homogenous form after shaking. Sediments formation have to be easily redispersed after shaking, forming homogenous suspension.

    Suspension comprises an active ingredient (solid phase) in a liquid carrier, a wetting agent, flavouring and colouring agents and preservatives.A wetting agent is used  to reduces surface tension between the particles and liquid. Suspension can be classified as a coarse suspension where the diameter of the particles is more than 1 µm or as 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.

Apparatus:

weighing balance

1weighing boat,
 mortar and pestle,
 plastic bottle 150ml,
 measuring cylinder 50ml,
 measuring cylinder 200ml,
 a set of pipette (1ml) and bulb-pipette,
 centrifugation tube 15ml,
 beaker 100ml,
 centrifugation equipment
 viscometer.

                      

Materials:

chalk

tragacanth

concentrated peppermint water

syrup BP

double-strength chloroform water

distilled water

Procedure

1 formulation of Pediatric Chalk Mixture (150 ml) was prepared by the following formulation.

Chalk	3 g
Tragacanth	(referred to the Table 1)
Concentrated Cinnamon Water	0.6 ml
Syrup BP	15 ml
Double Strength Chloroform Water	75 ml
Distilled Water, q.s.	150 ml

Table 1

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

1) 5 ml of suspension was poured into the weighing boat and labeled. Texture, clarity and color of the suspension formed was described and compared.

2) 50 ml of suspension was poured into 50 ml measurable cylinder. Height of the solid phase precipitated in the cylinder was measured at the interval of 0, 5, 10, 15, 20, 25, 30, 40, 50 and 60 minutes.

3) The rest of the suspension (95 ml) was poured into 100 ml beaker and the viscosity of the suspension was measured by a viscometer.

4) 10 ml of suspension was poured into centrifugator tube and the height of the solid phase was measured after centrifugation (1000rpm, 5 minutes, and 25°C)

Discussion

1) Compare the texture, clarity and colour of suspension.

GROUP 1: (0 tragacanth)

Texture: Smooth

Clarity: Two layers are form. The above layer is clear whereas the bottom layer is cloudy.

Colour: White

GROUP 2: (0 tragacanth)

Texture: Diluted

Clarity: Cloudy

Colour: Opaque white

GROUP 3: (0.1 tragacanth)

Texture: Smooth, dilute

Clarity: Initially, it is milky and not clear. After a time, it is cloudy and the suspended matter is visible.

Colour: White and transparent above the white layer

GROUP 4: (0.1 tragacanth)

Texture: Smooth

Clarity: Cloudy

Colour: White

GROUP 5: (0.3 tragacanth)

Texture: Viscous

Clarity: Cloudy

Colour: White

GROUP 6: (0.3 tragacanth)

Texture: Smooth texture, viscous, not easy sediment

Clarity: Cloudy

Colour: Milky white

GROUP 7: (0.5 tragacanth)

Texture: Very viscous, slightly smooth texture

Clarity: Cloudy

Colour: Milky

GROUP 8: (0.5 tragacanth)

Texture: Smooth texture, more viscous

Clarity: No sedimentation, cloudy

Colour: Milky white, one layer

Generally the colour of the suspension was white with cloudy clarity of suspension. For suspension without tragacanth, sedimentation takes place almost immediately due to absence of thickening agent. Rate of sedimentation increased with the use of thickening agent in the suspension. Use of greater amount of tragacanth resulted in longer time for the suspension to sediment. 

2) Graph height against time. Give a comment

Time (min)	0	5	10	15	20	25	30	35	40	45	50	55	60
Height (mm)	128	14	11	10	10	10	9	9	8	8	8	8	8

The graph shows the result for experiment without adding the tragacanth. So, the mixture without suspending agent results in rapid sedimentation due to instability.

3) Graph of height of sedimentation against time for suspension formulation that have different amount of  Tragacanth ingredient. Give a comment.

		Average height of sedimentation against time
Time (min)		0	5	10	15	20	25	30	35	40	45	50	55	60
	0.0	128	14	11	10	10	10	9	9	8	8	8	8	8
Amount of	0.1	120	90	40	40	40	40	40	40	40	40	40	40	40
Tragacanth (g)	0.3	121	121	121	120	120	119	119	119	119	119	119	119	119
	0.5	136	134	133	133	133	133	132	132	132	132	132	132	132

For both mixtures with 0.0g and 0.1g of tragacanth, the mixtures form sediment rapidly. The particles flocculate and form compact sediment or caking at the bottom. As the time goes, the height remains constant, indicate the equilibrium is reached. This also shows that 0.1g of tragacanth is not enough to act as suspending agent.

For experiment of 0.3g and 0.5g of tragacanth used, the height of sedimentation decrease slightly. This reflects the suitable amount of tragacanth used in the mixture, making it more stable and so the suspension particles take a longer time to flocculate.

4) Explain briefly the mechanism of viscometer analysis. Plot a graph of Viscosity (cP) against Tragacanth ingredient (g).


Formula for standard deviation: 

Amount of Tragacanth (g)	Viscosity (cP)						Viscosity (cP) (Average ± SD)
	1	2	3	4	5	6
0.0	2.50	3.60	3.40	2.20	2.10	4.40	3.03±0.83
0.1	5.00	3.00	4.00	5.00	5.00	4.00	4.33±0.75
0.3	7.00	6.50	6.00	6.00	6.00	8.00	6.58 ±0.73
0.5	3.00	4.70	5.90	4.00	5.90	5.90	4.90±1.12

Viscometer is an instrument used to measure the viscosity and flow parameters of The viscometer used in this experiment is rotational viscometer which measure the torque required to rotate a disk or bob in a fluid at a known speed. It 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 drag caused by relative motion of the fluid and a surface is a measure of the viscosity.

Here, tragacanth acts as the suspending agent.Besides acting as a suspending agent they also imparts viscosity to the solution. Suspending agents form film around particle and decrease interparticle attraction and act as thickening agents. They increase in viscosity of the solution, which is necessary to prevent sedimentation of the suspended particles as stated in Stokes law. Thus, suspending agents acts by reducing the movement (sedimentation) of suspended particles and physically stabilizing the product. A good suspension should have the following characteristics. At rest the solution is sufficiently viscous to prevent sedimentation and thus aggregation or caking of the particles. When agitation is applied to the suspension, its viscosity is reduced and can provide good flow characteristic to flow out from the mouth of bottle. Thus, increasing amount of suspending agent used will increased the viscosity of suspension.

According to the result above, for the viscosity of suspension containing 0.3g of tragacanth has higher viscosity than suspension containing 0.5g of tragacanth. This might be due to the errors when operating the viscometer. Theoretically the viscosity should be higher as the amount of tragacanth increase.  Firstly, maybe weight of Tragacanth does not weighed in precise quantity. Next,there might be an incomplete mixing of tragacanth and chalk. Then, maybe the spindle of viscometer did not washed completely before and after using the viscometer, that can lead to inaccurate reading.

5)Plot a graph sedimentation height after shaking versus tragacanth content

Shows that as increase the amount of wetting agent(g), the height of sedimentation will be decrease till reach the limit .It is because of wetting agent like tragacanth help to reduce interfacial tension of solute to miscible with solvent/vehicle. At certain limit when there is too excess of wetting agent can cause a little effect of flocculation that why can see the increase of height of sedimentation 

6) What is the functions of each substances used as excipients in suspenson formulation ?How different tragacanth content can affect the physical and stability of suspension formulation?

Chalk	Glidant	Improves the flowability of powder
Tragacanth	Suspending agent	Increase viscosity of vehicles and slow down sedimentation rates
Concentrated Peperminth Water	Flavouring agent	Masking the bad taste
Syrup BP	Suspending agent	Effectiveness as antimcrobial preservatives,reduces by chemical degradation and binding intraction with macromolecules
DOUBLE Strength Chloroform Water	Preservatives	Provide pleasant flavouring and prevent microbial growth
Distilled Water	Diluents	Increase bulk volume of powder

Tragacanth is used to suspend heavy insoluble powder.Thus it forms a viscous liquid(suspension) or gel depending on the concentration used.However,due to its natural products there is greater chance of microbial contamination.The low amount of tragacanth used cause low sedimentation rate.As if non tragacanth is added,the sedimentation occur rapidly after physical shake.If high amount of tragacanth is used,the sedimentation rates in suspension s increase allow reaching stability however if too much tragacanth causing forming gel –like suspension affect physical appearance

Conclusion

Solid particle not easily to dissolve/miscible in hydrophobic vehicle.It is because  presence of  interfacial tension between particle and vehicle so by reducing tension via use of wetting agent .By reducing the tension so increase the wettability,and decrease the height of settling form at bottom of measuring cyclinder.Example of wetting agent is tragacanth.If contact agent decrease less that 90 degree the particles will be float out from aqueos medium

References 

http://www.pharminfotech.co.nz/manual/Formulation/mixtures/vehicles.html

http://books.google.com.my/books?id=J5vE3Z_ZXJcC&pg=PA86&lpg=PA86&dq=tragacanth+in+suspensions&source=bl&ots=TIoQ-FYlzr&sig=PrXeMxvhKQiPpRvsLcW0m2rhkQU&hl=en&sa=X&ei=1iJeU6n3Cs7k8AWNj4DwCQ&redir_esc=y#v=onepage&q=tragacanth%20in%20suspensions&f=false