Pharmaceutical Emulsion

Course Dispersion, emulsion, Theories of emulsion, DLVO theory

1. Pharmaceutical Emulsions
(Dr.) Mirza Salman Baig
Assistant Professor (Pharmaceutics)
AIKTC, School of Pharmacy,NewPanvel
Affiliated to University of Mumbai (INDIA)

2. 2
Definition:An emulsion is a thermodynamically
unstable system containing mixture of two or
more immiscible liquids which is stabilized
by adding emulsifying agent
Emulsion

4. Phases in Emulsions:
➢One liquid is present as droplets distributed
throughout the other liquid
➢The dispersed liquid is known as theInternal or
Discontinuous phase.
➢Whereas the dispersion medium is known as
theExternal or Continuous phaseOilOil
Water
Water
Oil
Water
Agitation
Separate rapidly into two
clear defined layers
OilOil
Water
Water
Oil
Water
Agitation
Separate rapidly into two
clear defined layers

5. Types Of Emulsions
Based on dispersed phase:
➢Oil in Water (O/W): Oil droplets dispersed in water.
➢Water in Oil (W/O): Water droplets dispersed in oil.
➢Water in Oil in water (W/O/W): Water in Oil emulsion
dispersed in water –multiple emulsion.
Based on size of liquid droplets:
➢ 0.2 –50 mm →Macroemulsions
➢ 0.01 –0.2 mm →Microemulsions

6. Applications of Emulsion
•Oral administration of water insoluble
liquids (Fat soluble vitamins)
•Intravenous administration of API as an
emulsion (e.g. taxol)
•Emulsions for external use (E.g lotions,
liniments)
•Emulsions in aerosol can be used to
produce foam

7. Mechanism of action of
emulsifying agents
•When one liquid is broken in large no. of
small globules then interfacial area
increases
•Interfacial energy associated with interface
also increases
•To reduce interfacial energy, globules of
dispersed phase tends to coalesce
(merge)
•To prevent coalescence and to keep system
stable in disperse state it is necessary to
add emulsifying agent

8. Mechanism of action of emulsifying
agents
•Reduction of interfacial tension-
Thermodynamicstabilization
•Formation of interfacial filmbarrier
(stearic stabilization) Mechanical barrierto
coalescence
•Formation of electric double layer-
Electrical barrierto approach of globules

9. Thermodynamic stabilization of
emulsion
•Interfacial free energy (ΔG) in emulsion
•ΔG =γ
LLΔA
•γ
LLis interfacial tension
•Approaches for stable emulsion
•Reduceγ
LLby adding surface active agent
2019/4/17

10. Emulsifying Agents
•Emulsifying agent prevent coalescence of globules
of disperse by forming film around globules.
•An emulsifying agent is any material that enhances
the stability of an emulsion
•Emulsifying agents can be divided into 3 groups-
1.Surfactants (Surface active agents)
2.Hydrocolloids
3.Finely divided solids
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11. Emulsifying agents
(Theories of emulsification)
1) Surfactant (Monomolecular adsorption): To
reduce the interfacial tensionOil droplets are
surrounded by a coherent monolayer of the surfactant
which prevents coalescence. If the emulsifier is ionized,
the presence of strong charge may lead to repulsion in
droplets and hence increasing stability.
2) Hydrophillic Colloids (Multimolecular adsorption)
3) Finely divided solid particles (solid particles
adsorption): They are adsorbed at the interface
between two immiscible liquid phases to form
Particulate film.

12. Emulsifying agents (Mechanism of Action)Water
Oil

13. 1) Monomolecular Adsorption
•Amphiphiles (surfactants) reduce
interfacial tension (to 1 dyne/cm) because
of adsorption at interface o/w
•Droplets are sorrounded by coherent
monolayer that help prevent coalesence
(merging) between two droplets
•Surface Charge cause repulsion between
globules

14. Monomolecular Adsorption
(Combination of surfactants)
•Combination of surfactants is generally
used as it is more effective
•Combinnation of Sodium cetyl sulphate
and cholestrolleads to complex film that
produce excelent emulsion
•Hydrophilic Tween can be combined with
Lipophilic Span, varying proportions
produce desired emulsion... w/o or o/w

15. Surfactant / co-surfactant

16. Monomolecular Adsorption
(HLB)
•Type of emulsion produce depend on property of
emulsifying agents ... Hydrophilic lipophilic
balance (HLB)
•Type of emulsion is function of relative solubility
of the surfactant
•Rule of Bancroft: The phase (oil/water) in which
surfactant is relatively more soluble will become
continuous phase
•High HLB Surfactant prefer formation o/w
emulsion and vice versa

18. HLB
•A system was developed to assist in making
systemic decisions about the amounts and types
of surfactants needed in stable products.
•The system is called the HLB (hydrophile-
lipophile balance) systemand has an arbitrary
scale of 1 -18.
•HLB numbers are experimentally determined for
the different emulsifiers. .
Emulsifying agents
Surfactants

19. HLB valueApplication
1 -3 Anti-foaming agent.
3 -6 W/O emulsifying agents.
7 -9 Wetting agents.
8 -18 O/W emulsifying agents.
13 -15 Detergents.
15 -18 Solubilizing Agents.
Emulsifying agents
Surfactants
HLB

20. Emulsifying agents
(Surfactants Examples)
Anionicsurfactants:
•Theseareorganicsaltswhich,inwater,haveasurface-active
anion.E.g.
✓Alkalimetalandammoniumsoaps(saltsoflongchainfattyacids)such
assodiumstearateandpotassiumoleate(o/w).
✓Soapsofdivalentandtrivalentmetalssuchascalciumoleate(w/o).
✓Amineandammoniumsoapssuchastriethanolamineoleate(o/w).
✓Alkylsulphatessuchassodiumlaurylsulphate(SLS)(o/w).
Disadvantages:
•Theyareirritantinternallysowidelyusedinexternal
preparationsaso/wemulsifyingagents.
•anionicsurfactantsaregenerallystableatmorealkalinepH
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.

21. Cationicsurfactants:
•Theseareusuallyquaternaryammoniumcompounds
whichhaveasurface-activecation.
•Examplesincludecetrimideandbenzalkoniumchloride.
•Theyareusedinthepreparationofo/wemulsionsfor
externaluseandmustbeintheirionizedformtobe
effective.
•Thecationicsurfactantsalsohaveantimicrobialactivity.
•Disadvantages:
•Theyaresensitivetoanionicsurfactantsanddrugs.
•Emulsionsformedbyacationicsurfactantaregenerally
stableatacidicpH.
•Theyaremoretoxicthanothersurfactants.
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Emulsifying agents
(Surfactants Examples)

22. 2) Multimolecular Adsorption
(Hydrocolloids)
•Hydrophilic colloids (mucilage of gum
acacia) are different in action from
surfactants
•They do not cause lowring of interfacial
tension
•They form multimolecular layer at o/w
interface, action of hydrocolloids is
because of this reason
•They increase viscocity of dispersion
medium

23. Multimolecular film

24. Emulsifying agents
(Hydrocolloids Examples)
NaturalPolysaccharides:Themainproblemwiththese
agentsistheirnaturalvariabilitybetweenbatchesand
microbialcontamination.
•Thesematerialsshouldnotbeusedexternallyasthey
leaveastickyfeelontheskin.
•Acaciaisthebestemulsifyingagentforextemporaneously
preparedoralemulsionsasitformsathickfilmattheoil-
waterinterfacetoactasabarriertocoalescence.Itistoo
stickyforexternaluse.
•Tragacanthisusedtoincreasetheviscosityofan
emulsionandpreventcreaming.
•Otherpolysaccharides,suchasstarch,pectinand
carrageenan,areusedtostabilizeanemulsion.
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25. Semi-syntheticpolysaccharides:
•Thesearederivedfromthenaturallyoccurring
polysaccharidecelluloseandgenerallyformo/wemulsions.
•Examplesincludelow-viscositygradesof
✓Methylcellulose(MC)
✓Carboxymethylcellulose(CMC)
✓Hydroxypropylmethylcellulose(HPMC)
Synthetichydrocolloids:
✓Carbopol
✓Polyvinylalcohol(PVA).
✓Polyvinylpyrolidone(PVP)
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Emulsifying agents
(Hydrocolloids Examples)

26. 3) Solid Particles Adsorption
•Solid particles that can be wetted by oil as well
as water can act as emulsifying agent
•Their concentration is higher at interface
•They form particulate film around dispersed
droplets to prevent coalescence
•Example of agents: Bentonite
(Al
2O
3.4SiO
2.H
2O), Veegum(Magnesium
Aluminum Silicate)

27. Emulsifying agents
(Finely Divided Solid Example)
✓These agents form a particulate layer around
dispersed particles. These agents swell in the
dispersion medium to increase viscosityand
reduce the interaction between dispersed droplets.
Most commonly they support the formation of o/w
emulsions,
✓Bentonite
✓Veegum,
✓Hectorite,
✓Magnesium Hydroxide,
✓Aluminum Hydroxide
✓Magnesium Tri silicate.

28. Stability of
Emulsion

29. Stability problems
1.Sedimentationandcreaming.
2.Thermodynamicinstability(coalescenceorcracking).
3.Phaseinversion.
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31. Stability of emulsions
Creamingandsedimentation:
•Asthedisperseddropletsaresubjectedtogravityforce,theytendto
moveupward(creaming)ordownward(sedimentation)butnotboth.
•Creamingusuallyhappensino/wemulsions.
•Sedimentationusuallyhappensinw/oemulsion.
•TherateofsedimentationorcreamingisdescribedbyStoke’slaw.
•Wherev=velocityofsedimentationorcreamingofadispersed
particleofradiusr,anddensityσ,inaliquidofdensityρ,and
viscosityŋ,andwheregistheaccelerationduetogravity.
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32. Stability of emulsions
Creamingandsedimentation:
•Theprocessisreversibleandgentleshaking
redistributesthedropletsthroughoutthecontinuous
phase.
•However,creamingisundesirablebecause
✓itisinelegantandinaccuratedosingispossibleif
shakingisnotthorough.
✓Additionally,creamingincreasesthelikelihoodof
coalescenceofglobulesandthereforebreakdownof
theemulsionduetocracking.
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33. Stability of emulsions
Crackingorcoalescence:
•Emulsionsarethermodynamicallyunstablesystems;thereis
interfacialfreeenergy(IFE)(ΔG)betweenthetwophases.
•ΔG =γ
LLΔA
•γ
LLis interfacial tension
•Toenhancetheirstability,thedisperseddropletscomecloser
toeachotherandfuseinanattempttodecreasetheexposed
surfacearea.
•Coalescenceisthefusionoftwoormoredropletsofthe
dispersephaseformingonedroplet.
•Thisendsuptotheseparationofthedispersephaseasa
separatelayer(phaseseparation).
•Coalescenceisanirreversibleprocessandredispersion
cannotbeachievedbyshaking.
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34. Stability of emulsions
Howtoenhancestability(topreventcreamingand
cracking)?
•Globulesize:
✓Smallerparticleshaveslowercreamingorsedimentationthan
largerparticles(Stoke’slaw).
•Stableemulsionsrequireamaximalnumberofsmallsized(1-3
µm)globulesandasfewaspossiblelarger(>15µm)diameter
globules.
•Ahomogenizerwillefficientlyreducedropletsizebyforcingthe
emulsionthroughasmallaperturetoreducethesizeofthe
globules.
✓Additionally,reducingdropletsizemayadditionallyincreasethe
viscosityifmorethan30%ofdispersephaseispresent.
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35. Stability of emulsions
Howtoenhancestability(topreventcreamingand
cracking)?
•Viscosityofthecontinuousphase:
✓Increasingtheviscosityofthecontinuousphasewillreducethe
potentialforglobulecreamingandhencecoalescenceasthis
reducesthemovementofglobules.
✓Howtoincreaseviscosity?
❖Viscosityenhancingagents,whichincreasetheviscosityofthe
continuousphase,maybeusedino/wemulsions.e.g
tragacanth,sodiumalginateandmethylcellulose.
❖Higherpercentagesofoilphase(o/w).
❖Decreasingtheglobulesizeoftheinternalphase.
❖Higheramountsofsolidfatsintheoilyphase(i.e.highratiosof
solidfattoliquidfats).
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36. Stability of emulsions
Howtoenhancestability(topreventcreamingand
cracking)?
•Usingemulsifyingagents(hydrocolloids,surfactantsand
other):
✓Forminginterfacialfilmmechanicalbarrierwhichdecreasesthe
potentialforcoalescence(moreimportant).
✓Surfactantsmayreducetheinterfacialtensionbetweenthetwo
phases(lessimportant).
✓Hydrocolloidsenhancetheviscosityofthemedium.
Note:Careshouldbetakenforanyeffectsthatcouldaffectthe
interfacialfilm(chemical,physicalorbiologicaleffects).
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37. Stability of emulsions
Howtoenhancestability(topreventcreamingand
cracking)?
•Storagetemperature:
✓Extremesoftemperaturecanleadtoanemulsioncracking.
✓Whenwaterfreezesitexpands,sounduepressureisexerted
ondispersedglobulesandtheemulsifyingagentfilm,which
mayleadtocracking.
✓Conversely,anincreasedtemperaturedecreasestheviscosity
ofthecontinuousphaseanddisruptstheintegrityofthe
interfacialfilm.Anincreasingnumberofcollisionsbetween
dropletswillalsooccur,leadingtoincreasedcreamingand
cracking.
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38. Stability of emulsions
Phaseinversion
•Emulsiontypeisdeterminedby:
✓Theoiltowaterratio(amounts).
✓Thesolubilityoftheemulsifyingagent.
•Phaseinversionistheprocessinwhichanemulsionchanges
fromonetypetoanother,sayo/wtow/o.
•Themoststablerangeofdispersephaseconcentrationis30-
60%.Iftheamountofdispersephaseapproachesorexceeds
atheoreticalmaximumof74%ofthetotalvolume,thenphase
inversionmayoccur.
•Additionofsubstanceswhichalterthesolubilityofan
emulsifyingagentmayalsocausephaseinversion.
•Theprocessisirreversible.
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39. Methods for evaluation of
stability of emulsion
•Size frequency analysis over the time by
microscopic observation
•Velocity of creaming (as it is proportional to
droplet diameter)
•Globule size analysis using coulter-counting,
ultra centrifugal
•Turbidimetric analysis
•Thaw freeze cycle and centrifugation analysis
•Conductivity test during heating-cooling-heating
cycles

40. References
•P. J. Sinko, ‘Martin’s Physical Pharmacy and
Pharmaceutical Sciences’ Fifth edition,
Lippincott Williams and Wilkins, Indian Edition
distributed by B.I. Publications Pvt. Ltd, 2006
•Textbook of Physical Pharmaceutics, C.V.S
Subrahmanyum, Vallabh Prakashan

41. Thank You