slide1 n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Outcomes of this lecture PowerPoint Presentation
Download Presentation
Outcomes of this lecture

Loading in 2 Seconds...

play fullscreen
1 / 128

Outcomes of this lecture - PowerPoint PPT Presentation


  • 212 Views
  • Uploaded on

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.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Outcomes of this lecture' - shelley


Download Now An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
outcomes of this lecture
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

slide3

EMULSIONS

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).

slide4

To stabilize these droplets, emulsifying agent should be added

Microemulsion: Droplets size range 0.01 to 0.1 m m

Macroemulsion: Droplets size range approximately 5 m m.

general types of pharmaceutical emulsions
General Types of Pharmaceutical Emulsions:

1) Lotions

2) Liniments

3) Creams

4) Ointments

5) Vitamin drops

types of emulsion
Types of Emulsion

mm

Water

Oil

Oil-in-water emulsion

Water-in-oil emulsion

primary and secondary emulsion
Primary and secondary emulsion:
  • Primary emulsion containing one internal phase, for example, oil-in-water emulsion (o/w) and water-in-oil emulsion (w/o).
  • Secondary emulsion= multiple-emulsion: it contains two internal phase, for instance, o/w/o or w/o/w. It can be used to delay release or to increase the stability of the active compounds.
multiple emulsions
Multiple Emulsions

mm

Water

Oil

Water-in-oil-in-water emulsion

Oil-in-water-in-oil emulsion

emulsion size
< 0.5 mm

0.5-1.5 mm

1.5-3 mm

>3 mm

Emulsion Size
chemical composition
Chemical Composition

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

emulsion type and means of detection
Emulsion Type and Means of Detection:

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.

1 dilution test
1) Dilution Test:

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.

2 conductivity test
2) Conductivity Test:

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

3 dye solubility test
3) Dye-Solubility Test:
  • Water-soluble dye will dissolve in the aqueous phase.
  • Oil-soluble dye will dissolve in the oil phase.
4 fluorescence test
4-Fluorescence test:
  • oils give fluorescence under UV light, while water doesn’t. Therefore, O/W emulsion shows spotty pattern while W/O emulsion fluoresces.
pharmaceutical applications of emulsions
Pharmaceutical applications of emulsions:

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.

theories of emulsification
Theories of Emulsification:
  • Incase of two immiscible liquids
slide21
An explanation of this phenomenon is because of cohesive force between the molecules of each separate liquid exceeds adhesive force between two liquids. This is manifested as interfacial energy or tension at boundary between the liquids.
  • Therefore, to prevent the coalescence and separation, emulsifying agents have been used.
types of emulsifying agents
Types of emulsifying agents:

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

slide24
In emulsion, the surface area is high to maintain the dispersion of the droplets. Thus, based on the above equation surface free energy becomes high consequently. The only way to keep it low is to reduce the interfacial tension.

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.

slide26
The functions of surface active agents to provide stability to dispersed droplets are as following:

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

  • Combination of surface-active agents is used most frequently. The combination should form film that closely packed and condensed
classification of emulsifying surfactants
Classification of Emulsifying surfactants

1) Anionic group

2) Cationic group

3) Amphoteric group

4) Nonionic group

classification of surfactants
Classification of surfactants
  • The "tail" of most surfactants are fairly similar, consisting of a hydrocarbon chain, which can be branch, linear, or aromatic.
  • Fluorosurfactants have fluorocarbon chains.
  • Siloxane surfactants have siloxane chains.
classification of surfactants1
Classification of surfactants
  • Most commonly, surfactants are classified according to polar head group.
  • A non-ionic surfactant has no charge groups in its head.
  • The head of an ionic surfactant carries a net charge. If the charge is negative, the surfactant is more specifically called anionic; if the charge is positive, it is called cationic.
  • If a surfactant contains a head with two oppositely charged groups, it is termed zwitterionic.
anionic
Anionic
  • Sulfate, sulfonate, phosphate, and carboxylates. ammonium lauryl sulfate, sodium lauryl sulfate (SDS, sodium dodecyl sulfate, another name for the compound) and the related alkyl-ether sulfates sodium laureth sulfate, also known as sodium lauryl ether sulfate (SLES), and sodium myreth sulfate.
  • Docusates: dioctyl sodium sulfosuccinate, perfluorooctanesulfonate (PFOS), perfluorobutanesulfonate, linear alkylbenzenesulfonates (LABs).
anionic1
Anionic
  • Carboxylates

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).

cationic head groups
Cationic head groups
  • pH-dependent primary, secondary, or tertiary amines:

Primary amines become positively charged at pH < 10, secondary amines become charged at pH < 4:

    • Octenidinedihydrochloride;
cationic head groups1
Cationic head groups
  • Permanently charged quaternary ammonium cation:
    • Alkyltrimethylammonium salts: cetyltrimethylammonium bromide (CTAB) a.k.a. hexadecyltrimethyl ammonium bromide, cetyltrimethylammonium chloride (CTAC
    • Cetylpyridinium chloride (CPC)
    • Benzalkonium chloride (BAC)
    • Benzethonium chloride (BZT)
    • 5-Bromo-5-nitro-1,3-dioxane
    • Dimethyldioctadecylammonium chloride
    • Cetrimonium bromide
    • Dioctadecyldimethylammonium bromide (DODAB)
zwitterionic surfactants amphoteric
Zwitterionic surfactants (amphoteric)
  • The cationic part is based on primary, secondary, or tertiary amines or quaternary ammonium cations.
  • The anionic part can be more variable and include sulfonates, as in CHAPS (3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate).
  • Other anionic groups are sultaines illustrated by cocamidopropylhydroxysultaine. Betaines, e.g., cocamidopropylbetaine. Phosphates: lecithin
nonionic surfactant
Nonionic surfactant
  • Many long chain alcohols exhibit some surfactant properties.
  • Prominent among these are the fatty alcoholscetyl alcohol, stearyl alcohol, and cetostearyl alcohol (consisting predominantly of cetyl and stearyl alcohols), and oleyl alcohol.
nonionic surfactant1
Nonionic surfactant
  • Polyoxyethylene glycol alkyl ethers (Brij):

CH3–(CH2)10–16–(O-C2H4)1–25–OH:

- Octaethylene glycol monododecyl ether

  • Pentaethylene glycol monododecyl ether
  • Polyoxypropylene glycol alkyl ethers:

CH3–(CH2)10–16–(O-C3H6)1–25–O

nonionic surfactant2
Nonionic surfactant
  • Glucoside alkyl ethers:

CH3–(CH2)10–16–(O-Glucoside)1–3–OH:

- Decylglucoside,

- Laurylglucoside

- Octylglucoside

nonionic surfactant3
Nonionic surfactant
  • Polyoxyethylene glycol octylphenol ethers:

C8H17–(C6H4)–(O-C2H4)1–25–OH: Triton X-100

  • Polyoxyethylene glycol alkylphenol ethers:

C9H19–(C6H4)–(O-C2H4)1–25–OH:

  • Nonoxynol-9
  • Glycerol alkyl esters:

- Glyceryllaurate

nonionic surfactant4
Nonionic surfactant
  • Polyoxyethylene glycol sorbitan alkyl esters: Polysorbate
  • Sorbitan alkyl esters: Spans
  • Cocamide MEA, cocamide DEA
  • Dodecyldimethylamine oxide
  • Block copolymers of polyethylene glycol and polypropylene glycol: Poloxamers
  • Polyethoxylated tallow amine (POEA).
b multimolecular adsorption
B- Multimolecular adsorption
  • Hydrophilic colloids form multimolecular adsorption at the oil/ water interface. They have low effect on the surface tension.
  • Their main function as emulsion stabilizers is by making coherent multi-molecular film. This film is strong and resists the coalescence.
  • They have, also, an auxiliary effect by increasing the viscosity of dispersion medium.
slide42
Most of the hydrophilic colloids form oil-in-water emulsions.
  • Some of them can provide electrostatic repulsion like acacia, which contains Arabic acid and proteins (COOH and NH3)
c solid particle adsorption
C- Solid particle adsorption
  • Finely divided solid particles are adsorbed at the surface of emulsion droplet to stabilize them.
  • Those particles are wetted by both oil and water (but not dissolved) and the concentration of these particles form a particulate film that prevent the coalescence.
slide45
Particles that are wetted preferentially by water form o/w emulsion, whereas those wetted more by oil form w/o emulsion
  • Note that they are very rare to use and can affect rheology of the final product
  • Size of the particle is very important, larger particles can lead to coalescence
other emulsifying agents
Other emulsifying agents
  • Egg yolk:it contains phospholipids and cholesterol. The main withdraw back is that spoils quickly; therefore, it can’t be used in industry.
  • Wool fat:anhydrous lanolin, it is used to prepare w/o emulsion for external uses.
  • Starch:it forms starch mucilage and it is restricted for enemas preparation.
  • Cholesterol:it has stabilizing action; therefore, another emulsifier should be included.
criteria for the selection of emulsifying agents
CRITERIA FOR THE SELECTION OF EMULSIFYING AGENTS

An ideal emulsifying agent should posses the following characteristics:

  • It should be able to reduce the interfacial tension between the two immiscible liquids.
  • It should be physically and chemically stable, inert and compatible with the other ingredients of the formulation.
  • It should be completely non irritant and non toxic in the concentrations used.
  • It should be organoleptically inert i.e. should not impart any colour, odour or taste to the preparation.
  • It should be able to form a coherent film around the globules of the dispersed phase and should prevent the coalescence of the droplets of the dispersed phase.
  • It should be able to produce and maintain the required viscosity of the preparation.
selection of emulsifying agents using hlb method
Selection of Emulsifying Agents using HLB method

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

13-15 Detergents

10-18 Solubilizing agents

emulsifier with low hlb
Emulsifier with low HLB
  • An emulsifier having a low HLB number indicates that the number of hydrophilic groups present in the molecule is less and it has a lipophillic character.

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.

emulsifier with high hlb
Emulsifier with high HLB
  • A higher HLB number indicate that the emulsifier has a large number of hydrophilic groups on the molecule and therefore is more hydrophilic in character.

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.

disadvantage of the hlb system
DISADVANTAGE OF THE HLB SYSTEM

It does not take into account:

- the effect of temperature

- the presence of additives

- the concentration of emulsifier

hlb values of some common emulsifying agents
HLB values of some common emulsifying agents

Emulsifying Agent  HLB Value

Acacia: 8

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

how to control emulsion type during formulation
How to control emulsion type during formulation?
  • Volume of internal and external phases controls the type of emulsion.

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 and non-polar characteristic of emulsifying agents (relative solubility of emulsifying agent in water and oil).

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”.

what the factors that affect the choice of emulsion type
What the factors that affect the choice of emulsion type?

The choice of emulsion depends on:

(1)-properties and uses of final products

(2)- the other material required to be present.

  • Oil-soluble drug is prepared in o/w emulsion due its solubility and its taste can be masked by adding flavoring agents
  • For intravenous injection “ i.v.” o/w emulsion is the only type could be used.
  • For intramuscular injection “i.m.” both o/w and w/o types of emulsion could be used. Water-soluble drug can be prepared in w/o emulsion to get prolonged action (depot therapy)
  • Topical application:
    • Semisolid emulsions are called creams and lotions
difference between o w and w o emulsions
DIFFERENCE BETWEEN O/W AND W/O EMULSIONS

Oil in water emulsion

  • Water is the dispersion medium and oil is the dispersed phase
  • For insoluble drug
  • For local effect
  • Easily to wash from skin
  • Doesn’t have greasy texture of oily preparation
  • Acceptable by consumer
  • They are used externally to provide cooling effect e.g. vanishing cream
  • Water soluble drugs are more quickly released from o/w emulsions
  • They are preferred for formulations meant for internal use as bitter taste of oils can be masked.
difference between o w and w o emulsions contin
DIFFERENCE BETWEEN O/W AND W/O EMULSIONS (Contin…)

Water in oil emulsion

  • Oil is the dispersion medium and water is the dispersed phase
  • For water soluble drug
  • Can be use to hydrate the upper layer of stratum corneum (moisturizing cream)
  • Can increase the absorption of drug from these formulation
  • Can be used to clean skin from dirt
  • Oil soluble drugs are more quickly released from w/o emulsions
  • They are preferred for formulations meant for external use like creams.
  • Not acceptable by consumer
properties of emulsion
Properties of emulsion

The basic properties which should be present in an emulsion include:

  • appearance,
  • feel,
  • odour,
  • desirable viscosity,
  • consistency,
  • effectiveness,
  • stability.

These properties depends on the:

  • ingredients,
  • type of emulsion,
  • ratio of the two phases,
  • type and quantity of emulsifying agents,
  • method of emulsification .
slide59
O/w emulsions will generally have a sheen or matte surface as compared to w/o emulsions which have a shiny or oily surface due to the presence of oil as external phase.

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

methods for preparing emulsions for internal use
Methods for preparing Emulsions for Internal use

1- Trituration Method

This method consists of dry gum method and wet gum method.

  • Dry 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.

  • Wet Gum Method

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.

slide61
2- Bottle Method
  • This method is employed for preparing emulsions containing volatile and other non-viscous oils.
  • Both dry gum and wet gum methods can be employed for the preparation.
  • As volatile oils have a low viscosity as compared to fixed oils, they require comparatively large quantity of gum for emulsification.
  • In this method, oil or water is first shaken thoroughly and vigorously with the calculated amount of gum. Once this has emulsified completely, the second liquid (either oil or water) is then added all at once and the bottle is again shaken vigorously to form the primary emulsion. More of water is added in small portions with constant agitation after each addition to produce the final volume.
methods of preparation of emulsions
Methods of Preparation of Emulsions:

1) Continental or Dry Gum Method:

"4:2:1" 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.

2 english or wet gum method
2) English or wet Gum Method:

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.

3 bottle or forbes bottle method
3) Bottle or Forbes Bottle Method:

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

points to be considered during formulations of emulsions
Points to be considered during formulations of emulsions
  • Stability of the active ingredient
  • Stability of the excipients
  • Visual appearance
  • Color
  • Odor (development of pungent odor/loss of fragrance)
  • Viscosity, extrudability
  • Loss of water and other volatile vehicle components
points to be considered continued
Points to be considered… (Continued)
  • Concentration of emulsifier
  • Order of addition of ingredients Particle size
  • distribution of dispersed phases
  • pH
  • Temperature of emulsification
  • Type of equipment
  • Method and rate of cooling
points to be considered continued1
Points to be considered… (Continued)
  • Texture, feel upon application (stiffness, grittiness, greasiness, tackiness, spreadibility)
  • Microbial contamination/sterility (in the unopened container and under conditions of use)
  • Release/bioavailability (percutaneous absorption)
  • Phase distribution, Phase Inversion (homogeneity/phase separation)
quality control tests for emulsions
Quality control tests for Emulsions

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.

quality control tests contin
Quality control tests….(Contin..)

3. Determination of viscosity:

  • The viscometers which should be used include cone and plate viscometers. Capillary and falling sphere type of viscometrs should be avoided.
  • For viscous emulsions, the use of penetrometer is recommended as it helps in the determination of viscosity with age.
  • In case of o/w emulsions, flocculation of globules causes an immediate increase in viscosity. After this change, the consistency of the emulsion changes with time.
  • In case of w/o emulsions, the dispersed phase particles flocculate quite rapidly resulting in a decrease in viscosity, which stabilizes after 5 to 15 days.
  • As a rule, a decrease in viscosity with age reflects an increase of particle size due to coalescence.
quality control tests contin1
Quality control tests….(Contin..)

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.

instabilities in emulsions
Instabilities In Emulsions
  • An emulsion is a thermodynamically unstable preparation so care has to be taken that the chemical as well as the physical stability of the preparation remains intact throughout the shelf life.
  • There should be no appreciable change in the mean particle size or the size distribution of the droplets of the dispersed phase and secondly droplets of the dispersed phase should remain uniformly distributed throughout the system.
emulsion destabilization
Emulsion Destabilization
  • Creaming
  • Flocculation
  • Coalescence
  • Combined methods
instabilities in emulsions con
Instabilities In Emulsions…(Con..)

1- Creaming

  • An emulsion is said to cream when the oil or fat rises to the surface, but remains in the form of globules, which may be redistributed throughout the dispersion medium by shaking.
  • An oil of low viscosity tends to cream more readily than one of high viscosity.
  • Increasing the viscosity of the medium decreases the tendency to cream.
  • Creaming is a reversible phenomenon which can be corrected by mild shaking.
creaming
Creaming

Buoyancy

(Archimedes)

h Continuous phase viscosity

Dr density difference

g Acceleration due to gravity

ddroplet diameter

v droplet terminal velocity

vs Stokes velocity

Friction

(Stokes-Einstein)

instabilities in emulsions con1
Instabilities In Emulsions…(Con..)

The factors affecting creaming are best described by strokeâs law:

V= 2r2 (d1-d2) g/9η

Where; V= rate of creaming

r=radius of globules

d1= density of dispersed phase

d2= density of dispersion medium

g= gravitational constant

η = viscosity of the dispersion medium

the following approaches can be used for decreasing creaming
The following approaches can be used for decreasing Creaming
  • Reduction of globule size:

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.

  • Increasing the viscosity of the continuous phase:

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.

instabilities in emulsions con2
Instabilities In Emulsions…(Con..)

2- Cracking

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:

  • addition of an incompatible emulsifying agent,
  • chemical or microbial decomposition of emulsifying agent,
  • addition of electrolytes,
  • exposure to increased or reduced temperature,
  • change in pH.
instabilities in emulsions con3
Instabilities In Emulsions…(Con..)

3- Phase Inversion

  • In phase inversion o/w type emulsion changes into w/o type and vice versa.
  • It is a physical instability.
  • It may be brought about by the addition of an electrolyte or by changing the phase volume ratio or by temperature changes.

Phase inversion can be minimized by:

  • using the proper emulsifying agent in adequate concentration,
  • keeping the concentration of dispersed phase between 30 to 60 %
  • storing the emulsion in a cool place.
instabilities in emulsions con4
Instabilities In Emulsions…(Con..)

4- Breaking:

  • Separation of the internal phase from the external phase is called BREAKING of the emulsion.
  • All or part of the liquid of the internal phase becomes "unemulsified on the top or bottom of the emulsion.
  • This is irreversible
instabilities in emulsions con5
Instabilities In Emulsions…(Con..)

5- Aggregation:

  • The internal phase tends to form aggregates of globules.
  • Large globules or aggregates of globules rise to the top or fall to the bottom of the emulsion to form a concentrated layer of the internal phase.
flocculation and coalescence
Flocculation and Coalescence

Collision and

sticking (reaction)

Stir or change chemical conditions

FLOCCULATION

Rehomogenization

Film rupture

COALESCENCE

rheology of flocculated emulsions
Flocculation leads to an increase in viscosity

Water is trapped within the floc and must flow with the floc

Effective volume fraction increased

Rheology of Flocculated Emulsions

rg

gelled emulsions
Gelled Emulsions

Thin liquid

Viscous liquid

Gelled solid

slide84

Creaming & Slight Flocculation

  • Flocs have larger effective size
  • Smaller Dr
  • Tend to cream much faster
slide85

Creaming & Extreme Flocculation

  • Heavily flocculated emulsions form a network
  • Solid-like properties (gel)
  • Do not cream (may collapse after lag period)
preservation of emulsions
Preservation Of Emulsions

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:

  • color and odor change,
  • gas production,
  • hydrolysis,
  • pH change,

and eventually breaking of emulsion

an ideal preservative
An ideal preservative
  • should be nonirritant, nonsensitizing and nontoxic in the concentration used.
  • It should be physically as well as chemically compatible with other ingredients of the emulsions and with the proposed container of the product.
  • It should not impart any taste, color or odor to the product.
  • It should be stable and effective over a wide range of pH and temperature.
  • It should have have a wide spectrum of activity against a range of bacteria, yeasts and moulds.
  • The selective preservative should have high water solubility and a low oil/water partition coefficient.
  • It should have bactericidal rather than bacteriostatic activity.
examples of antimicrobial preservatives used to preserve emulsified systems
Examples of antimicrobial preservatives used to preserve emulsified systems:
  • parahydroxybenzoate esters such as methyl, propyl and butyl parabens,
  • organic acids such as ascorbic acid and benzoic acid,
  • organic mercurials such as phenylmercuric acetate phenylmercuric nitrate,
  • quarternary ammonium compounds such as cetrimide,
  • cresol derivatives such as chlorocresol
  • miscellaneous agents such as sodium benzoate, chloroform and phenoxyethanol.
preservation of emulsions con
Preservation Of Emulsions… (Con.)

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.

  • Antioxidants are agents having a high affinity for oxygen and compete for it with labile substances in the formulation.
the ideal antioxidant should be
The ideal antioxidant should be
  • nontoxic,
  • nonirritant,
  • effective at low concentration under the expected conditions of storage and use,
  • soluble in the medium and stable.
  • Antioxidants for use in oral preparation should also be odorless and tasteless.

Some of the commonly used antioxidants for emulsified systems include:

  • alkyl gallate such as ethyl, propyl or dodecyl gallate,
  • butylated hydroxyanisole (BHA),
  • butylated hydroxytoluene (BHT)
stability testing
Stability testing

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:

  • Centrifugal force
  • Agitational force
  • Aging
  • Temperature
slide92
The following physical parameters are evaluated to assess the effect of any of the above stress conditions:
  • Phase separation
  • Viscosity
  • Electrophoretic properties
  • Particle size and particle count
packaging labelling and storage of emulsions
Packaging, Labelling And Storage Of Emulsions
  • Depending on the use, emulsions should be packed in suitable containers.
  • Emulsions meant for oral use are usually packed in well filled bottles having an air tight closure.
  • Light sensitive products are packed in amber coloured bottles.
  • For viscous emulsions, wide mouth bottles should be used.
packaging labelling and storage of emulsions1
Packaging, Labelling And Storage Of Emulsions
  • The label on the emulsion should mention that these products have to be shaken thoroughly before use.
  • External use products should clearly mention on their label that they are meant for external use only.
  • Emulsions should be stored in a cool place but refrigeration should be avoided as this low temperature can adversely effect the stability of preparation
routes of administration of emulsions
Routes of administration of emulsions

Oral Emulsions:

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.

liquid paraffin oral emulsion
Liquid Paraffin Oral Emulsion
  • Liquid Paraffin 500 ml
  • Methyl cellulose 20 g
  • Vanillin 0.5 g
  • Chloroform 2.5 ml
  • Benzoic acid solution 20 ml
  • Saccharin sodium 0.05 g
  • Purified Water q.s 1000ml

Uses: Laxative. It acts as an emollient purgative in chronic constipation especially during pregnancy and old age.

castor oil emulsion
Castor oil Emulsion
  • Castor oil 16 ml
  • Gum acacia q.s
  • Water 80 ml

Uses: Purgative

cod liver oil emulsion
Cod-Liver oil Emulsion
  • Cod-liver oil 30 ml
  • Syrup 12 ml
  • Ferric ammonium citrate 4 g
  • Cinnamon water q.s. 90 ml

Uses: Source of vitamin A and D.

topical emulsions
Topical Emulsions:
  • For external use, emulsions may be either o/w or w/o type.
  • Emulsions finds the maximum use in topical preparations , both for therapeutic and cosmetic use.
  • Therapeutically they are used as carrier for a drug.
  • In cosmetic industry o/w emulsions have been used for formulation of moisturing lotions, hand lotions and make up foundation lotions.
  • When oily layers are desired to prevent moisture loss from the surface of skin, for barrier action and for cleansing action, then w/o emulsions are formulated like cold creams.
antiseptic cream
Antiseptic cream
  • Cetrimide 1g
  • Cetostearyl alcohol 10 g
  • White soft paraffin 10 g
  • Liquid paraffin 29 g
  • Purified water 50 g

Uses: Antiseptic cream for the treatment of cuts, wounds and burns.

cold cream
Cold Cream
  • Liquid paraffin 20 g
  • Hard paraffin 4.5 g
  • Lanette wax 3.5 g
  • Glycerine 4.5 g
  • Water 17.5 g
  • Propyl paraben 0.1 g

Uses: Skin protective and skin smoothner.

briefing
Briefing

Types Of Emulsions

  • Oil in water emulsions
  • Water in oil emulsions
  • Multiple emulsions
  • Microemulsions
oil in water emulsions o w
Oil in water Emulsions (O/W):
  • In this emulsion oil is the dispersed phase and water is the dispersion medium.
  • The common example is milk.
  • These emulsions are used mainly for internal/oral use as bitter or disagreeable taste and odor of drugs can be masked by emulsification.
  • Externally these emulsions are used for formulating non greasy creams, lotions and liniments.
  • Cosmetic products prepared using o/w emulsions can easily be removed from the surface of the skin
  • Example: Castor oil emulsion, foundation creams, vanishing creams.
water in oil emulsions w o
Water in oil Emulsions (W/O):
  • In this emulsion water is the dispersed phase or the internal phase and oil is the dispersion medium or the external phase.
  • They are mainly used externally as lotions and creams as the external layer of oil forms an occlusive layer and prevents the evaporation of moisture from the surface of the skin.
  • They are also effective as cleansing cream as they solubilize the oil soluble dirt from the surface.
  • Example: Cold creams.
multiple emulsions1
Multiple Emulsions :
  • In this emulsion, oil in water (o/w) or water in oil emulsion (w/o)s is dispersed in another liquid medium to produce oil in water in oil (o/w/o) emulsion or water in oil in water (w/o/w) emulsion.
  • Multiple emulsions are primarily used for formulating sustained release dosage forms as the drug entrapped in the innermost layer has to pass through the other two phases before being released for absorption.
microemulsions
Microemulsions:
  • Microemulsions are thermodynamically stable clear isotropic solution of oil, water and amphiphile (Emulsifying agent).
  • They are homogeneous in nature.
  • They contain globules having a diameter ranging from 0.1 to 100 micrometers.
  • These emulsions appear as transparent solutions and are more acceptable physically as compared to conventional emulsions.
advantages of emulsions
Advantages 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.

advantages of emulsions1
Advantages of 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.

clinical uses of emulsions
Clinical Uses of Emulsions

1. Oral (Liquid administration of oils, eg. Vitamins A, D, and E) Reasons of use:

  • No oily mouth-feel (if an o/w emulsion is used).
  • Better taste than if completely solubilized.
  • May be more bioavailable.
  • Solubilized drug may be more bioavailable
clinical uses of emulsions1
Clinical Uses of Emulsions

2. Parenteral Drug Solubilization:

  • Emulsification of oils.
  • Emulsification of lipids for parenteral nutrition.
clinical uses of emulsions2
Clinical Uses of Emulsions

3. Topical

  • O/W emulsions: Drug suspended or solubilized in the oil phase; less greasy than petrolatum type bases; no occlusion.
  • W/O emulsions: some occlusive effect but slightly less greasy than the petrolatum bases.
fluorescence test
Fluorescence Test

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

cobalt chloride test
Cobalt Chloride Test

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.

types of emulsifying agents1
Types of emulsifying agents:

1) Surface active agent:

forming a monomolecularfilm

2) Hydrophilic colloids:

forming a multimolecularfilm

3) Finely divided solid particles:

forming a particulate film

emulsions preparation methods
Emulsions Preparation Methods

1- Trituration Method

  • Dry Gum Method
  • Wet Gum Method

2- Bottle Method

emulsions quality control tests
Emulsions Quality control tests

1. Determination of particle size and particle count:

2. Determination of phase separation

3. Determination of viscosity

4. Determination of electrophoretic properties

slide128
Hope you be a good

Emulsion Maker