preformulations

1. Presented By : Facilitated To:
Sachin.J.Gaddimath Mr. Avinash.S.G
M.Pharm 1st year Asst. Professor
Dept. of Pharmaceutics Dept. of Pharmaceutics
HSKCOP, BAGALKOT. HSKCOP, BAGALKOT
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2. Contents
 Emulsion Definition
1.Theories of Emulsification
2.Method of preparation of Emulsion
3.Instability of Emulsion
 Suspension Definition
1.Method of preparation of Suspension
2.Preparation techniques for Suspension
3.Stability of suspension
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3. Emulsion:
 A thermodynamically unstable system consisting
of at least 2 immiscible liquid phases, 1 of which
is dispersed as globules in the other liquid phase.
 The dispersed liquid is known as the internal or
discontinuous phase.
 Where as the dispersed medium is known as the
external or continuous phase.
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4. Theories of Emulsification:
 Many theories have been advanced to account for the
way or means by which the emulsion is stabilized by
the emulsifier.
1.Electric Double Layer Theory.
2.Phase Volume Theory.
3.Hydration Theory of Emulsions.
4.Oriented wedge theory.
5.Adsorbed Film and Interfacial tension Theory.
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5. 1.Electric Double Layer Theory:
 layer of oppositely charged ions forms a layer in the
oil globules in a pure oil and pure water emulsion
carry a negative charge. The water ionizes so that both
hydrogen and hydroxyl ions are present.
 The negative charge on the oil may come from
adsorption of the OH ions.
 These adsorbed hydroxyl ions form a layer around the
oil globules. A second liquid outside the layer of
negative ions.
 The electric charge is a factor in all emulsions, even
those stabilized with emulsifying agents.
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6. 2.Phase Volume Theory:
 If spheres of same diameter are packed as closely as
possible, one sphere will touch 12 others and the
volume the spheres occupy is about 74 per cent of the
total volume.
 Thus if the spheres or drops of the dispersed phase
remain rigid it is possible to disperse 74 parts of the
dispersed phase in the continuous phase; but if the
dispersed phase is increased to more than 74 parts of
the total volume, a reversal of the emulsion will occur.
 However, the dispersed phase does not remain rigid in
shape but the drops flatten out where they come in
contact with each other, nor are all the dispersed
particles the same.
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7. 3.Hydration Theory of Emulsions:
 Fischer and Hooker state that hydrated colloids make
the best emulsifiers.
 Fischer states the emulsifying agent, by which a
permanent emulsion is obtained, "proves to be a
hydrophilic colloid when water and oil emulsions are
concerned.
 Fischer and Hooker have found albumin, casein, and
gelatin to be good emulsifying agents.
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8. 4.Oriented wedge theory:
 This theory deals with formation of monomolecular layers
of emulsifying agent curved around a droplet of the
internal phase of the emulsion.
Example:
 In a system containing 2 immiscible liquids, emulsifying
agent would be preferentially soluble in one of the phases
and would be embedded in that phase.
 Hence an emulsifying agent having a greater hydrophilic
character will promote o/w emulsion and vice-versa.
 Sodium oleate is dispersed in water and not oil. It forms a
film which is wetted by water than by oil. This leads the
film to curve so that it encloses globules of oil in water.
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9. 5.Adsorbed film & interfacial tension theory:
 Lowering interfacial tension is one way to decrease the
free surface energy associated with the formation off
droplets. Assuming the droplets are spherical,
ΔF= 6 γV/ D
 Where,
 V= volume of the dispersed phase in ml,
 D= Mean diameter of the particles.
 γ= interfacial tension
 It is desirable that the surface tension should be
reduced below 10dynes /cm by the emulsifier and it
should be absorbed quickly.
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10. Methods of Preparation Of Emulsions:
 Commercially, emulsions are prepared in large volume
mixing tanks and refined and stabilized by passage
through a colloid mill or homogenizer.
Extemporaneous production is more concerned with
small scale methods.
Methods:
1.Dry Gum Method
2.Wet Gum Method
3.Bottle Method
4.Beaker Method
5.In situ Soap Method
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11. 1.DRY GUM Method:
 Dry gum method is used to prepare the initial or primary
emulsion from oil, water, and a hydrocolloid or "gum" type
emulsifier.
 Dry Gum Methodology (4 parts oil, 2 parts water, and 1
part Emulsifier).
Procedure:
 Take mortar, 1 part gum is levigated with the 4 parts oil
until the powder is thoroughly wetted; then the 2 parts
water are added all at once, and the mixture is vigorously
triturated until the primary emulsion formed is
creamy white and produces a "cliking" sound as it is
triturated.
 Active ingredients, preservatives, colour, flavours are
added as a solution to the primary emulsion.
 When all agents have been incorporated, the emulsion
should be transferred to a calibrated vessel, brought to
final volume with water.
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12. 2.Wet Gum Method:
 Methodology
 (Oil 4 parts + Water 2 parts + Emulsifier 1 parts)
Procedure:
 In this method, the proportions of oil, water, and
emulsifier are the same (4:2:1), but the order and
techniques of mixing are different.
 The 1 part gum is triturated with 2 parts water to form
a mucilage; then the 4 parts oil is added slowly, in
portions, while triturating.
 After all the oil is added, the mixture is triturated for
several minutes to form the primary emulsion.
 Then other ingredients may be added as in the
continental method.
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13. 3.Bottle Method:
 This method may be used to prepare emulsions of
volatile oils, Oleaginous substances of very low
viscosities.
 This method is a variation of the dry gum method.
 One part powdered acacia (or other gum) is placed in
a dry bottle and four parts oil are added.
 The bottle is capped and thoroughly shaken.
 To this, the required volume of water is added all at
once, and the mixture is shaken thoroughly until the
primary emulsion forms.
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14. 4.Beaker Method:
 Dividing components into water soluble and oil
soluble components.
 All oil soluble components are dissolved in the oily
phase in one beaker and all water soluble components
are dissolved in the water in a separate beaker.
 Oleaginous components are melted and both phases
are heated to approximately 70°C over a water bath.
 The internal phase is then added to the external phase
with stirring until the product reaches room
temperature.
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15. 5.In situ Soap Method:
 Two types of Soaps developed by this Methods:
 Calcium Soaps
 Soft Soaps
 1) Calcium Soaps: W/O type Emulsions.
 E.g. Oleic acid + Lime water. Prepared by simple
mixing of equal volumes of Oil and Lime water.
 Emulsifying agent used is Calcium salt of free fatty
acids.
 E.g. Olive Oil + Oleic acid (FAA)
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16.  Instability in Emulsion:
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Instability Factors Prevention
Flocculation :
Globules come closes to each
other to form aggregates.
1) Uniform globule size
distribution.
2) Opposite charge on
globule surface.
3) Low viscosity of external
medium.
1) Uniform sized globules.
2) Use same charged ionic
electrolytes.
3) Viscosity improving agents
hydrocolloids.
Creaming:
Concentration of globules at
top/bottom of emulsion.
1. Globule size.
2. Viscosity of external
medium.
3. Differences in density of
oil-water
(aq >oil).
1. Homogenization
uniformed sized globules.
2. Thickening agents to
improve viscosity.
3. Reducing density
differences
(Bromoform+oil).
Coalescence:
Few globules fuse to form
bigger globules emulsifier film
is destroyed.
1. Insufficient amount of E.A
2. Altered partitioning of E.A
3. Incompatibility between
E.A
4. Phase volume ratio > than
74%.
NO this is permanent change

17. Instability Factors Prevention
Breaking:
Complete separation of oil &
aqueous phases
Unnoticed coalescence NO this is permanent change
Phase inversion:
Change in emulsion from o/w
to w/o or vice versa
1. Change in chemical nature
of E.A→ Sodium
sterate(water soluble)
→o/w emulsion.
Sodium sterate + CaCl2 →
Calcium sterate
Calcium sterate(oil soluble) →
w/o emulsion.
1. Altering phase: volume
ration
o/w emulsion +oil → w/o
emulsion + water → o/w this
method should be properly
controlled otherwise lead to
the phase inversion.
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18. Suspension:
 A pharmaceutical suspension is a coarse dispersion in
which internal phase is dispersed uniformly
throughout the external phase.
Method of Preparation of suspension:
Suspension can be prepared by 2 methods :
 Precipitation methods:
 Dispersion method:
Precipitation methods:
Three main methods
 Organic solvent precipitation
 Precipitation effected by changing pH of the medium
 Double decomposition
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19.  Organic solvent precipitation:
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20.  Precipitation effected by changing pH of the
medium:
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21.  Double decomposition:
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22.  Dispersion method:
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23. Preparation techniques of suspension:
 Small scale preparation of suspensions
 Large scale preparation of suspensions
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24. Small scale preparation of suspensions:
Grinding insoluble materials with vehicle containing the
wetting agent
↓
Soluble ingredients are dissolved in same portion of the
vehicle
↓
Added to the smooth paste to step1 to get slurry.
↓
Make up the dispersion to the final volume.
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25. Large scale preparation of suspensions:
 If suspension is made by dispersion process it is best to
achieve pulverization of solid by micronization
technique or spray drying
 If suspension is made by controlled crystallization, a
supersaturated solution should be formed and then
quickly cooled with rapid stirring.
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26. Stability of suspension:
1)Small particle size:
Reduce the size of the dispersed particle
increase the total surface area of the solid. The greater
the degree the subdivision of a given solid the larger
the surface area.
The increase in surface in surface area means
also an liquids leading to an increase in viscosity of a
system.
2) Temperature:
Another factor which negatively affects the stability
and usefulness of pharmaceutical suspensions is
fluctuation of temp..
Temperature fluctuations can lead caking of claying.
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27. 3.Increasing the viscosity:
 Increasing the viscosity of the continuous phase can
lead to the stability of suspension this is so because the
rate of sedimentation can be reduce by increase in
viscosity.
 Viscosity increase is brought about by addition of
thickening agents to the external phase. In water these
must be either soluble or swell.
 It is important to note that the rate of release of a drug
from a suspension is also dependent on viscosity of a
product.
 The more viscous the preparation, the slower Is likely
to be the release of a drug sometimes this property
may be desirable for depot preparations.
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28. REFERENCE
1. Leon Lachmann,HerbertA. Lieberman. The Theory &
Practice of Industrial Pharmacy. 2009 Edition.
2. Text book of Physical Pharmacy by Alfred Martin,
Varghese publication.
3. Text book of Modern Pharmaceutics by Gilbert &Banker.
4. Text book of pharmaceutical practice by M .Alton.
Pharmaceutical dosage forms.
5. Pharmaceutical preformulation by J.T.Carstensen, Ph.D
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29. THANK YOU
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