1. Dr. Mohammad Javed Ansari, PhD.
COLLEGE OF PHARMACY
PHARMACEUTICS II
(PHT 312)
Disperse system
&
EMULSIONS
Dr. Mohammad Javed Ansari, PhD.
Contact info:
Deptt of Pharmaceutics, COP, PSAU, Al-kharj

2. objectives of the lecture
At the end of this lecture, you will be aware of:
What are disperse systems?
What are various types of disperse systems?
What are emulsions?
What are various types emulsions?
Why emulsions are thermodynamically unstable?
What are various stability problems?
How emulsions are stabilized?
What are emulsifying agent / emulgents?
What are various types of emulgents?
How emulgent stabilize the emulsion?
What are advantages / disadvantages of emulsions?
How emulsions are prepared?

3. Disperse Systems

4. Disperse systems

5. Thermodynamically unstable because of immiscible phases.
Emulsion
BIPHASIC LIQUID DOSAGE FORM consisting of one liquid phase dispersed as globules/droplets (dispersed phase or internal phase) within a second immiscible liquid phase (continuous phase/ external phase).
Thermodynamically unstable because of immiscible phases.
These system are stabilized by using emulsifying agents.
Emulsifying agents Reduce interfacial surface tension
Dispersed phase
Continuous phase

6. THEORY OF EMULSIFICATION
What happens when 2 immiscible liquids are agitated together?
One of the liquids is dispersed as small droplets in the other.
But after a while !
The liquids separate rapidly into
two clearly defined layers
WHY?
A fine dispersion of oil and water leads to an enormous increase in the interfacial area.
This is associated by an increase in the interfacial free energy also known as surface free energy.
This phenomenon leads to the system is thermodynamically unstable.
The high interfacial free energy favors a reduction of interfacial area by causing droplets to coalesce. Therefore separation of phases takes place.

7. THEORY OF EMULSIFICATION
SURFACE FREE ENERGY: The work W required to create a unit area of surface is known as SURFACE FREE ENERGY/UNIT AREA (ergs/cm2).
Thus the greater the area A of interfacial contact between the phases, the greater the free energy.
SURFACE FREE ENERGY is equivalent to the surface tension γ.
Therefore to decrease surface free energy we can decrease surface tension by adding surfactants/emulgent or emulsifying agents.
Work W = F × d (force multiplied by distance ), γ =F/2L,
(γ surface tension, is the force per unit length) F= γ × 2L
W = γ × 2L × d (since 2L × d is equal to the increase in surface area ΔA).
W = γ ΔA (ΔA is increase in area for a finite work.
∆E = OW X ∆ A

8. THEORY OF EMULSIFICATION: How Emulgents Work?
Emulsifier – The Stabilizer
Lipophilic Tail & Hydrophilic Head
Lipophilic tails align with oil
Hydrophilic heads align with water
Emulsifying agents stabilize emulsions by 3 mechanisms:
1. Reduction of interfacial tension.
3. Formation of an electric double layer-
electric barrier to approach of particles.
2. Formation of a rigid interfacial film-
mechanical barrier to coalescence

9. ∆E = SL * ∆ A THEORY OF EMULSIFICATION: How Emulgents Work?
1. Reduction of interfacial tension.
∆E = SL * ∆ A
2. Formation of a rigid interfacial film-mechanical barrier to coalescence.
If the concentration of the emulsifier is high enough, it forms a rigid film between the immiscible phases, which hinders mechanically the coalescence of the emulsion droplets.
3. Formation of an electric double layer- electric barrier to coalescence.
In case of an ionic surfactant, the hydrocarbon tail is dissolved in the oil droplet, while the ionic heads are facing the continuous aqueous phase.
As a result, the surface of the droplet is charged. This creates a repulsive effect between the oil droplets and thus hinders coalescence. +

10. THEORY OF EMULSIFICATION: HOW EMULSIONS ARE STABILIZED?

12. CLASSIFICATION OF EMULSIONS
Based on nature of dispersed phase
Oil in Water (O/W): Oil droplets dispersed in water.
Water in Oil (W/O): Water droplets dispersed in oil.
Based on size of dispersed phase /droplets.
>1000 nm Macroemulsions
10 – 200 nm Microemulsions
Based on Number of dispersed phase: Multiple emulsion
W/o/w (water in oil in water): Small water droplets are enclosed within larger oil droplets which are themselves then dispersed in water
O/w/o (oil in water in oil): Small oil droplets are enclosed within larger water droplets which are themselves then dispersed in oil phase

14. CLASSIFICATION OF EMULSIONS

15. Oil in Water – O/W Dispersed phase / Internal phase = OIL Advantages
Dispersion medium/ continuous phase /External phase = WATER
Advantages
Easiest to formulate
disperses more easily
has consistent pH
Least expensive
Best feel – cooling effect
Disadvantages
Less oil delivered
Not as effective for dry skin
Not water-resistant
Examples: Hair conditioners, Sunscreen, vanishing cream, Wrinkle Creams, Mayonnaise, milk, cream and butter.

16. Advantages Disadvantages Water in Oil – W/O
Dispersed phase / Internal phase = WATER
Dispersion medium/ continuous phase /External phase=WATER
Advantages
Waterproofing possible
Most effective for dry skin
Better stability
Disadvantages
Oily, tacky feel
More expensive
Examples: COLD CREAMS

17. Multiple Emulsions Multiple phases Advantages Disadvantages
Oil in Water in Oil (O/W/O)
Water in Oil in Water (W/O/W)
Advantages
More effective than Oil in Water
Less greasy than Water in oil
Time release, active delivery possible
Disadvantages
Difficult to manufacture
Not always stable

18. PHARMACEUTICAL APPLICATIONS OF EMULSION
Masking of unpleasant taste: Most important application of emulsion is for masking the disagreeable taste of oily liquids by formulating them as o/w emulsions. For e.g. some vitamins.
Increase the absorption: Emulsions of oils like liquid paraffin and olive oil enhance the rate and extent of their absorption from the alimentary canal due to fine state of subdivisions.
Topically applied:
Medicinal agents that are irritating to the skin are less
irritating if present in the internal phase of emulsion.
Cold cream and vanishing creams are a emulsion which are used externally.
More acceptable than greasy products (ointments).

19. PHARMACEUTICAL APPLICATIONS OF EMULSION
Parenteral administrations
Emulsions have been used for the intravenous administrations of lipid nutrients.
w/o emulsions have been employed to disperse water soluble antigenic materials in mineral oil for intramuscular depot injection.
Aerosol
Emulsification is used in aerosol to produce foams
Prolonged Action
These products can also be used for the prolonged release of drugs that are incorporated into the internal aqueous phase.

20. Formulation aspects: Elements of the Formula
Formula Components
Oil Phase
Hydrophobic materials: Oils, fats, lipids
Affects viscosity, spread,
Aqueous phase
Extracts, colorants
Humectants
Thickeners
Emulsifiers
Holds it all together

21. Types of Emulsifying agents
Synthetic
Anionic
Alkali soaps
Amine soaps
Sulphated comp.
Corboxylated compds
Cationic
Quaternary ammonium compounds
Cetrimide
Cetylpyridinium chloride
Benzalkonium chloride
AMPHOTERIC
Aminoacids
Betains
Lecithin
Nonionic
Glycerol esters
Sorbitan esters
Polysorbates
Higher fatty alcohol
Natural

22. Types of Emulsifying agents
e.g. Sodium stearate
Sodium lauryl sulfate
Triethanolamine stearate
Eg. Cetrimide, Cetylpyridinium chloride
Benzalkonium chloride
Eg. Betains,
Aminoacids,
Lecithin
Cetyl and stearyl alcohols
Glyceryl monostearate
Sorbitan esters of fatty acids (Spans)
Polyethylene glycol derivatives of the sorbitan esters (Tweens)

23. Non-ionic surfactants
Most non-ionic surfactants are based on:
A fatty acid or alcohol (usually with carbon atoms), the hydrocarbon chain of which provides the hydrophobic part.
An alcohol (-OH) and/or ethylene oxide group (-OCH2CH2-) which provide the hydrophilic part of the molecule.
Advantages
They have greater degree of compatibility than do anionic and cationic emulgents.
Less sensitive to changes in pH & electrolytes.
They are very useful for parenteral and oral administration because of their low toxicity and irritancy.

24. Non-ionic surfactants
Sorbitan esters of fatty acids (Spans)
Sorbitan is esterified with lauric, palmitic, stearic or oleic fatty acid.
Variations in the type of fatty acid produce different Spans:
Span 20 with lauric acid (sorbitan monolaurate)
Span 40 with Palmitic acid (sorbitan monopalmitate)
Span 60 with stearic acid (sorbitan monostearate)
Span 80 with oleic acid (sorbitan monooleate)
Polysorbates (Tweens)
Polyethylene glycol derivatives of the sorbitan esters (Polyoxtethylene sorbitan ester of fatty acids).
Variations in the type of fatty acid produce different tweens chain with different oil and water solubility, (Tween 20, 40, 60 and 80).
Advantages of tweens:
Compatible with other types of surfactants.
Stable to heat, pH change and electrolytes.
Low toxicity, for oral and parenteral preparations.
Disadvantages:
Unpleasant taste.
Inactivate some preservatives as parabenze by complexation

25. NATURAL EMULSIFIERS
Only acacia is regarded as primary emulsifier. The rest are used mainly as emulsion stabilizer. They produce o/w emulsions.
A- Acacia: Its mucilage allow the oil to be sheared into finely divided globules. However acacia is not viscous enough to prevent rapid rise of globules (creaming) thus sometimes thickening agents e.g. agar or tragacanth are added.
B- Tragacanth & Sodium alginate: The emulsifying ability is due to the high viscosity of its mucilage.
C- Polysaccharides: They form at the oil/water interface a multi-molecular layer that act as a barrier to coalescence.
D- Starch:Is a poor emulsifying agent. It acts by increasing the viscosity of continuous phase. It is used for preparation of enemas containing oil.

26. Hydrophilic-Lipophilic Balance (HLB) System
Emulsifiers / Surfactants are characterized according to the "balance" between the hydrophilic ("water-loving") and lipophilic ("oil-loving") portions of their molecules.
The hydrophilic-lipophilic balance (HLB) number indicates the polarity of the molecules in a range of 1-40, with the most commonly used emulsifiers having a value between 1 and 20.
The HLB number increases with increasing hydrophilicity.
According to the HLB number, surfactants may be utilized for different purposes:
          Function        HLB Range       
  Antifoaming agent           
Emulsifier, (w /o)              
Wetting agent               
Emulsifier, (o/ w)              
  Detergent            
Solubilizer       
1-3
3-6
7-9
8-18
13-15
15-18

27. Emulsifiers – HLB system
HLB tells about varying degrees of non-polar & polar character.
Specific oils need emulsifier with specific HLB (polar/non-polar character) to be effectively emulsified.
Emulsifiers should have similar HLB values to that of the respective oils in order to achieve maximum stabilization.
Less polar (low HLB)
More Polar (High HLB)
Common Oils used and the HLB needed to
Create an emulsion

28. Hydrophilic-Lipophilic Balance (HLB) System
The desired HLB numbers can also be achieved by mixing lipophilic and hydrophilic surfactants.
William Griffin devised HLB System to calculated amount of emulsifier to get the desired HLB.
Advantage of HLB system:
Gives stable emulsion.
Works best with nonionic surfactants.
Disadvantage:
HLB is only a good approximation.
Doesn’t always work. .

29. WHAT ARE OTHER ADDITIVES IN EMULSIONS?
Preservatives
Antioxidants
Humectants
Density modifiers
Buffers
Flavors and sweetening agents

30. Preservatives Low o/w partition coefficient.
Free from toxicity, color, odor and taste.
Effective in present of other ingredients and in wide range
of pH and temperature.
Types of preservative
Parahydroxybenzoic acid esters:
Methyl, ethyl, propyl, butyl esters are effective at pH 7-9.
Organic mercurial compounds:
Phenyl mercuric nitrate and acetate effective in emulsions
containing non-ionic emulgents.
Organic acids:
Used in acidic pH (Benzoic and Sorbic acids).

31. Preservatives…… Humectants Quaternary ammonium compounds:
Cetrimide Emulsifying and preservative agent ineffective against gram –ve bacteria and bacterial spores.
Chlorocresol:
For external preparations, its activity reduce at pH and in
presence of vegetable oils.
Humectants
Propylene glycol, glycerol and sorbitol (5%).
Reduce the evaporation of water from opened package or from the skin.
At high concentration they cause dehydration and remove moisture from the skin.

32. Antioxidants
Oxidation of vegetable oils cause its rancidity with unpleasant odor and appearance
They are classified into:
True Antioxidants (oil soluble)
E.g. Butylated hydroxy anisole, Butylated hydroxy toluene,
L-tocopherol (Vitamin E).
they capable of involvement in free radical process, protecting the
oil from involvement.
Reducing agents:
E.g. Sodium metabisulfate, Cystein HCl , Ascorbic acid (Vitamin C).
EDTA as chelating agent retard the oxidation reaction as it
chelate metal ions that catalyze oxidation process.

33. Methods of Emulsion Preparation:
On a small scale, emulsions may be prepared using:
A dry porcelain mortar and pestle.
A mechanical blender or mixer.
A simple prescription bottle.
On a large scale
Mechanical stirrer
High speed impeller in large volume mixing tanks may be used to form the coarse emulsion.
Homogenizers
The dispersion of two liquid is achieved by forcing their mixture through a small inlet orifice at high pressure.
colloid mill
Colloid mill operate on the principle of high shear, which is generated between the rotor and the stator of the mill.

34. Methods of Emulsion Preparation:
Lab methods used by the community pharmacist.
1- The continental or dry gum method
the emulsifying agent (usually acacia) is mixed with the oil before the addition of water.
2- The English or wet gum method
the emulsifying agent is added to the water. (In which It Is soluble) to form a mucilage, and then the oil is slowly incorporated to form the emulsion
3- The bottle or the Forbes bottle method
The bottle method is reserved for volatile oils or less viscous oils.
Powdered acacia + 2 part of oil are placed in a dry bottle and the mixture is thoroughly shaken.
A volume of water approximately equal to the oil is then added in portions, the mixture being thoroughly shaken after each addition the primary emulsion thus formed may be diluted to the proper volume with water.

35. Methods of Emulsion Preparation:
Bancroft's rule:
Emulsion type depends more on the nature of the emulsifier than on the relative proportions of oil or
water present
the methodology of preparing emulsion.
The phase in which an emulsifier is more soluble constitutes the continuous phase
In O/W emulsions – emulsifying agents are more soluble in water than in oil (High HLB surfactants).
In W/O emulsions – emulsifying agents are more soluble in oil than in water (Low HLB surfactants).
The order of addition of the phases
W O + emulsifier W/O
O W + emulsifier O/W.

38. Tests for Identification of Emulsion Type
Miscibility tests with oil or water
The emulsion will only be miscible with liquids that are miscible with its continuous phase.
Conductivity measurements
Systems with aqueous continuous phases will readily conduct electricity, whereas systems with oily continuous phases will not since most oils are poor conductors
o/w or w/o ???

39. Staining tests O/W emulsion W /O emulsion
If a water-soluble dyes is added in an o/w emulsion the emulsion takes up the color uniformity, phase is continuous phase.
Conversely if the emulsion is w/o type and dye being soluble in water, the emulsion takes up the color only in the dispersed phase and the emulsion is not uniformly colored.
O/W emulsion
W /O emulsion

40. Wetting of Filter Paper Method
Fluorescence Method
Many oils fluoresce under ultraviolet light. Thus, if the whole field fluoresces under fluorescent light microscope, the emulsion is wl o, if, on the other hand, only a few fluorescent dots are evident, the emulsion is o/w.
O/W emulsion
W /O emulsion
Wetting of Filter Paper Method
This method depends on the respective abilities of oil and water to wet filter paper. A drop of the emulsion is placed on a piece of filter paper; if the liquid spreads rapidly, leaving a small drop at the center, the emulsion is o/w. If no spreading occurs, the emulsion is w/o.

41. Stability of Emulsions
What are the characteristics of a stable emulsion?
A stable emulsion is one in which:
-dispersed globules retain their initial character
-and remain uniformly distributed throughout the continuous phase.
Thus change in number of dispersed globules
Change in size of globules
Change in globule size distribution (polydispersity index)
and change in viscosity means unstable emulsions.

42. Physical Instability of emulsions
Deptt of Pharmaceutics, COP, SAU, Al-kharj

43. Physical Instability: Creaming and Sedimentation
This process results from external forces, usually gravitational or centrifugal.
When such forces exceed the thermal motion of the droplets (Brownian motion), a concentration gradient builds up in the system such that the larger droplets move more rapidly either to the top resulting in CREAMING (if their density is less than that of the medium)
or to the bottom resulting in SEDIMENTATION (if their density is greater than that of the medium) of the container.

44. Physical Instability: Creaming & sedimentation
Creaming and sedimentation results temporary changes of emulsion into two regions, one of which is richer in the disperse phase than the other e.g. the creaming of milk, when fat globules slowly rise to the top of the product.
Creaming and sedimentation are reversible process.
Velocity of the creaming and sedimentation is governed by Stokes’ law
g = gravity constant
r = radius of the dispersed globules
 = viscosity of the external phase
 = density of the internal phase
o= density of the external phase
v = velocity of sedimentation of the dispersed spherical particles
From this this law it is clear that velocity is directly proportional to
density difference between the both phase, and radius of the globules.
Inversely proportional to viscosity of the external phase.
2 r2 ( - o) g
9 
V =

45. B- Coalescence (Breaking, Cracking)
Process of thinning and disruption of the liquid film between the droplets, with the result that fusion of two or more droplets occurs to form larger droplets.
Cracking or coalescence of an emulsion leads to the separation of dispersed phase as a layer.
Cracking is a irreversible process (permanent loss) .

46. Preventing Coalescence (Breaking, Cracking)
The coalescence of oil globules in an o/w emulsion is resisted by the presence, of a mechanically strong adsorbed layer of emulsifier around each globule.
This is achieved by the presence of either a condensed mixed monolayer of lipophilic and hydrophilic emulgents, or a multimolecular film of a hydrophilic material.

47. Physical Instability: Flocculation & Ostwald ripening
Flocculation : Aggregation of the droplets (without any change in primary droplet size) into larger units.
Flocculation occurs when there is not sufficient repulsion to keep the droplets apart at distances where the van der Waals attraction is weak.
Ostwald Ripening (Disproportionation) : Aggregation of the droplets with change in primary droplet size.
With emulsions which are usually polydisperse, the smaller droplets will have a greater solubility when compared to larger droplets (due to curvature effects).
With time, the smaller droplets disappear and their molecules diffuse to the bulk and become deposited on the larger droplets.

48. Physical Instability: Inversion of Emulsions
(Phase inversion)
O/W W/O
Nature of emulsifier: Making the emulsifier more oil soluble tends to produce a W/O emulsion and vice versa. (Bancroft's rule)
Phase volume ratio
Oil/Water ratio  W/O emulsion and vice versa.
Temperature of the system:  Temperature of O/W makes the emulsifier more hydrophobic and the emulsion may invert to W/O.
Addition of electrolytes and other additives: Addition of Strong electrolytes to O/W (stabilized by ionic surfactants) may invert to W/O
Example. Inversion of O/W emulsion (stabilized by sodium cetyl
sulfate and cholesterol) to a W/O type upon addition of polyvalent Ca.

49. 2- Chemical Instability of Emulsion
1) Chemically incompatibility of the emulgent system with the active agent and with the other emulsion ingredients
Ionic emulsifying agents are usually incompatible with materials of opposite charge. i. e. anionic and cationic emulgents .
Addition of electrolyte may cause salting out of the emulsifying agent or phase inversion e.g. sodium soap stabilize o/w emulsion so when a divalent electrolyte such as CaCl2 is added it may form the calcium soap, which stabilize a w/o emulsion.
Emulgents may also be precipitated by the addition of materials in which they are insoluble e.g. precipitation of hydrophilic colloids by the addition of alcohol.
Changes in pH may also lead to the breaking of emulsions. Sodium soaps may react with acids and produce the free fatty acid and the sodium salt of the acid. Soap-stabilized emulsions are therefore usually formulated at an alkaline pH.

50. 2- Chemical Instability of Emulsion
2) Oxidation
Many of the oils and fats used in emulsion formulation are of animal or vegetable origin and can be susceptible to oxidation by:
Atmospheric oxygen or .
By the action of microorganisms.
The resulting rancidity is manifested by the formation of degradation products of unpleasant odour and taste.
This can be controlled by the use of:
Antioxidants.
Antimicrobial preservatives.

51. 2- Chemical Instability of Emulsion….
3) Microbiological Contamination
Microbial contamination may causes:
Gas production.
Colour and odour changes.
Hydrolysis of fats and oils.
pH changes in the aqueous phase.
Breaking of the emulsion.
Why it happens?
Some of the hydrophilic colloids (emulsifying agents) may provide a suitable nutritive medium for microorganisms.
Most fungi and many bacteria will multiply readily in the aqueous phase of an emulsion.
o/w emulsions tend to be more susceptible to microbial spoilage than w/o products, why? In w/o emulsions the continuous oil phase acts as a barrier to the spread of microorganisms throughout the product, and the less water there is present the less growth there is likely to be.
Therefore an antimicrobial agent must be added.

52. 2- Chemical Instability of Emulsion….
4) Adverse Storage Conditions
Increase in temperature will causes:
An increase in the rate of creaming, due to a fall in
apparent viscosity of the continuous phase.
increased kinetic motion of the dispersed droplets thus the
number of collisions between globules will increase
The emulsifying agent at the oil/water interface will result
in a more expanded monolayer, and so coalescence is more
likely.
Certain macromolecular emulsifying agents may be
coagulated.
Decrease in temperature may cause:
Precipitation of certain emulgents.

53. Stability Testing of Emulsions
1) Macroscopic Examination
Examination of the degree of creaming or coalescence occurring over a period of time.
This is carried out by calculating the ratio of the volume of the creamed or separated part of the emulsion and the total volume.
2) Globule Size Analysis
Microscopic examination - Coulter counter - laser diffraction sizing are most widely used to determine the mean globule size as an increase with time is a sign for coalescence.
3) Viscosity Changes
Any variation in globule size or number or in the orientation or migration of emulsifier over a period of time may be detected by a change in apparent viscosity.
In order to compare the relative stabilities of similar products it is often necessary to speed up the processes of creaming and coalescence by temperature cycling or centrifugation.

54. Emulsions Emulsion suitable for intravenous injection.
Balm: Water in oil emulsion
Sodas: Oil in Water emulsion
Milk: Oil in Water emulsion
Dodecane droplets in a continuous phase of water/glycerol mixture.
Mayonnaise: Oil in Water emulsion

55. Emulsions encountered in everyday life!
Metal cutting oils
Margarine
Ice cream
Pesticide
Asphalt
Skin cream

56. THANK YOU FOR ATTENTION
GOOD LUCK ..
April 25, 2017
Deptt of Pharmaceutics, COP, SAU, Al-kharj