Outcomes of this lecture. 1- Definition and Classification of Emulsion 2- Pharmaceutical and medical application of Emulsion 3- Theories of Emulsification 4- Formulation of Emulsion 5- Emulsifying agants 6- Stability of suspensions & Quality control. EMULSIONS.
1- Definition and Classification of Emulsion
2- Pharmaceutical and medical application of Emulsion
3- Theories of Emulsification
4- Formulation of Emulsion
5- Emulsifying agants
6- Stability of suspensions & Quality control
An emulsion is liquid preparation containing two immiscible liquids, one of which is dispersed as globules
(dispersed phase = internal phase)
in the other liquid
(continuous phase = external phase).
Microemulsion: Droplets size range 0.01 to 0.1 m m
Macroemulsion: Droplets size range approximately 5 m m.
5) Vitamin drops
Interfacial layer. Essential to stabilizing the emulsion
Oil Phase. Limited effects on the properties of the emulsion
Aqueous Phase. Aqueous chemical reactions affect the interface and hence emulsion stability
using of naked eye, it is very difficult to differentiate between o/w or w/o emulsions.
Thus, the four following methods have been used to identify the type if emulsions.
based on the solubility of external phase of emulsion.
- o/w emulsion can be diluted with water.
- w/o emulsion can be diluted with oil.
water is good conductor of electricity whereas oil is non-conductor. Therefore, continuous phase of water runs electricity more than continuous phase of oil.
= Bulb glows with O/W
= Bulb doesn’t glow with W/O
1 ) To mask the taste
2) O/W is convenient means of orally administration of water-insoluble liquids
3) O/W emulsion facilitates the absorption of water-insoluble compounds comparing to their oily solution preparations (e.g. vitamins)
4) Oil-soluble drugs can be given parentrally in form of oil-in water emulsion. (e.g Taxol)
5) Emulsion can be used for external application in cosmetic and therapeutic uses.
1) Surface active agent: adsorbed at oil/water interface to form monomolecular film to reduce the interfacial tension
2) Hydrophilic colloids: forming a multimolecular film around the dispersed droplet
3) Finely divided solid particles: they are adsorbed at the interface between two immiscible liquid phases to form particulate film
Surface active agent (SAA) is molecule which have two parts, one is hydrophilic and the other is hydrophobic. Upon the addition of SAA, they tend to form monolayer film at the oil/water interface.
1) Reduction of the interfacial tension
2) Form coherent monolayer to prevent the coalescence of two droplet when they approach each other
3) Provide surface charge which cause repulsion between adjust particles
1) Anionic group
2) Cationic group
3) Amphoteric group
4) Nonionic group
These are the most common surfactants and comprise the alkyl carboxylates (soaps), such as sodium stearate. More specialized species include sodium lauroylsarcosinate and carboxylate-based fluorosurfactants such as perfluorononanoate, perfluorooctanoate (PFOA or PFO).
Primary amines become positively charged at pH < 10, secondary amines become charged at pH < 4:
- Octaethylene glycol monododecyl ether
C8H17–(C6H4)–(O-C2H4)1–25–OH: Triton X-100
An ideal emulsifying agent should posses the following characteristics:
A system was developed by William C. Griffin to assist making systemic decisions about the amounts and types of surfactants needed in stable products. The system is called the HLB (hydrophile-lipophile balance) system.
HLB RANGE USE
0-3 Antifoaming agents
4-6 W/O emulsifying agent
7-9 Wetting agents
8-18 O/W emulsifying agent
10-18 Solubilizing agents
For example, spans generally have low HLB number and they are also oil soluble. Because of their oil soluble character, spans cause the oil phase to predominate and form a w/o emulsion.
Tweens have higher HLB numbers and they are also water soluble. Because of their water soluble character, tweens will cause the water phase to predominate and form an o/w emulsion.
It does not take into account:
- the effect of temperature
- the presence of additives
- the concentration of emulsifier
Emulsifying Agent HLB Value
Polysorbate 20 (Tween 20): 16.7
Polysorbate 60: (Tween 60): 14.9
Polysorbate 80 (Tween 80): 15
Oleic acid: 4.3
Sorbitan monolaurate (Span 20): 8.6
Sorbitan monolaurate (Span 60): 4.7
Sorbitan monolaurate (Span 80): 4.3
The smaller volume will be for the internal phase and the larger volume will be for external phase. In some cases, internal phases can be more than 50% of the total volume.
Dominance of polar part results in formation of o/w emulsion and dominance of non-polar part results in formation of w/o emulsion. Note that polar groups are better barriers than non-polar; therefore, o/w emulsion can be prepared with more than 50 % of oil phase “ internal phase”.
The choice of emulsion depends on:
(1)-properties and uses of final products
(2)- the other material required to be present.
Oil in water emulsion
Water in oil emulsion
The basic properties which should be present in an emulsion include:
These properties depends on the:
W/o emulsios are oily and greasy in nature, not easily removable from the surface of the skin whereas o/w emulsions are non greasy and easily removable from the skin surface.
The viscosity of the emulsions depends generally on the viscosity of the continuous phase. As the ratio of dispersed phase increases, the viscosity also increases to a point where emulsion starts loosing its fluidity
1- Trituration Method
This method consists of dry gum method and wet gum method.
In this method the oil is first triturated with gum with a little amount of water to form the primary emulsion. The trituration is continued till a characteristic ‘clicking’ sound is heard and a thick white cream is formed. Once the primary emulsion is formed, the remaining quantity of water is slowly added to form the final emulsion.
As the name implies, in this method first gum and water are triturated together to form a mucilage. The required quantity of oil is then added gradually in small proportions with thorough trituration to form the primary emulsion. Once the primary emulsion has been formed remaining quantity of water is added to make the final emulsion.
1) Continental or Dry Gum Method:
4 parts (volumes) of oil
2 parts of water
1 part of gum
Acacia or other o/w emulsifier is triturated with oil in a perfectly dry Wedgwood or porcelain mortar until thoroughly mixed.
Glass mortar has too smooth a surface to produce the proper size reduction of the internal phase (Do not use glass mortar).
After the oil and gum have been mixed, the two parts of water are then added all at once and the mixture is triturated immediately.
Mucilage of the gum is prepared by triturating acacia (or other emulsifier) with water.
The oil is then added slowly in portions, and the mixture is triturated to emulsify the oil.
Should the mixture become too thick during the process, additional water may be blended into the mixture before another successive portion of oil is added.
Useful for extemporaneous preparation of emulsion from volatile oils or oleaginous substance of low viscosity.
1- Put powdered acacia in a dry bottle.
2- Add 2 parts of oil
3- Thoroughly shake the mixture in the capped bottle.
4- A volume of water approximately equal to the oil is then added in portions, the mixture being thoroughly shaken after each addition.
This method is not suitable for high viscous oils
1. Determination of particle size and particle count:
It is performed by optical microscopy, sedimentation by using Andreasen apparatus and Coulter counter apparatus.
2. Determination of phase separation:
Phase separation may be observed visually or by measuring the volume of the separated phases.
3. Determination of viscosity:
4. Determination of electrophoretic properties:
Determination of electrophoretic properties like zeta potential is useful for assessing flocculation since electrical charges on particles influence the rate of flocculation.
O/W emulsion having a fine particle size will exhibit low resistance but if the particle size increase, then it indicates a sign of oil droplet aggregation and instability.
h Continuous phase viscosity
Dr density difference
g Acceleration due to gravity
v droplet terminal velocity
vs Stokes velocity
The factors affecting creaming are best described by strokeâs law:
V= 2r2 (d1-d2) g/9Î·
Where; V= rate of creaming
r=radius of globules
d1= density of dispersed phase
d2= density of dispersion medium
g= gravitational constant
Î· = viscosity of the dispersion medium
According to strokeâs law, rate of creaming is directly proportional to the size of globules. Bigger is the size of the globules, more will be the creaming. Therefore in order to minimize creaming, globule size should be reduced by homogenization.
Rate of creaming is inversely proportional to the viscosity of the continuous phase i.e. more the viscosity of the continuous phase, less will the problem of creaming. The viscosity of the continuous phase should be increased by adding suitable viscosity enhancers like gum acacia, tragacanth etc.
Occasionally, it happens that an emulsion cracks during preparation, i.e., the primary emulsion does not become white but acquires an oily translucent appearance. In such a case, it is impossible to dilute the emulsion nucleus with water and the oil separates out.
Cracking of emulsion can be due to:
3- Phase Inversion
Phase inversion can be minimized by:
Stir or change chemical conditions
1- Preservation from microorganisms:
It is necessary to preserve the emulsions from microorganisms as these can proliferate easily in emulsified systems with high water content, particularly if carbohydrates, proteins or steroidal materials are also present.
Contamination due to microorganisms can result in problems such as:
and eventually breaking of emulsion
2- Preservation from oxidation:
Oxidative changes such as rancidity and spoilage due to atmospheric oxygen and effects of enzymes produced by micro-organisms is seen in many emulsions containing vegetables and mineral oils and animal fats.
Some of the commonly used antioxidants for emulsified systems include:
Stability testing of emulsions involves determining stability at long term storage conditions, accelerated storage conditions, freezing and thawing conditions. Stress conditions are applied in order to speed up the stability testing.
The stress conditions used for speeding up instability of emulsions include:
Generally o/w emulsions are used for internal use as the oil is more readily absorbed in a fine state of subdivision through the gastro intestinal tract and secondly the preparation becomes more palatable when water forms the continuous phase, as the medicinal oil is enveloped in a thin film of emulgent which masks the bitter and oily taste of the drug like liquid paraffin.
Orally emulsions are also used to facilitate the absorption of the oil soluble drugs like vitamins A,D, E and K.
Uses: Laxative. It acts as an emollient purgative in chronic constipation especially during pregnancy and old age.
Uses: Source of vitamin A and D.
Uses: Antiseptic cream for the treatment of cuts, wounds and burns.
Uses: Skin protective and skin smoothner.
Types Of Emulsions
1. They can mask the bitter taste and odor of drugs, thereby making them more palatable. e.g. castor oil, cod-liver oil etc.
2. They can be used to prolong the release of the drug thereby providing sustained release action.
3. Essential nutrients like carbohydrates, fats and vitamins can all be emulsified and can be administered to bed ridden patients as sterile intravenous emulsions.
4. Emulsions provide protection to drugs which are susceptible to oxidation or hydrolysis.
5. Intravenous emulsions of contrast media have been developed to assist in diagnosis.
6. Emulsions are used widely to formulate externally used products like lotions, creams, liniments etc.
1. Oral (Liquid administration of oils, eg. Vitamins A, D, and E) Reasons of use:
2. Parenteral Drug Solubilization:
If an emulsion on exposure to ultra-violet radiations shows continuous florescence under microscope, then it is w/o type and if it shows only spotty fluorescence, then it is Oil in o/w type
When a filter paper soaked in cobalt chloride solution is added to an emulsion and dried, it turns from blue to pink, indicating that the emulsion is o/w type.
1) Surface active agent:
forming a monomolecularfilm
2) Hydrophilic colloids:
forming a multimolecularfilm
3) Finely divided solid particles:
forming a particulate film
1- Trituration Method
2- Bottle Method
1. Determination of particle size and particle count:
2. Determination of phase separation
3. Determination of viscosity
4. Determination of electrophoretic properties