Emulsion - Physical Pharmacy

Physical Pharmacy Notes ppt.

1. EMULSION
•Anemulsionmaybedefinedasabiphasicsystemconsisting
oftwoimmiscibleliquidsoneofwhich(thedispersed
phase)isfinelysubdividedanduniformlydispersedas
dropletsthroughouttheother(thecontinuousphase).
•Sincesuchasystemisthermodynamicallyunstable,a
suitableemulsifyingagentisrequiredtostabilizethe
system.
•Thedispersedphaseorcontinuousphasecanrangein
consistencyfromamobileliquidtoasemi-solid.
•Thuspharmaceuticalemulsifiedsystemsrangefromlotions
andoralemulsionsofrelativelylowviscositytoointments
andcreamswhicharesemi-solidinnature.
•Theparticlesizeofthedispersedphasegenerallyranges
from0.1to100m.

2. Types of Emulsion
1.Oil-in-Water Emulsions:
•Inpharmaceuticalemulsions,onephaseisusuallywaterand
theotheranoil,fatorwaxysubstance.
•Systemsinwhichoilisthedispersedordiscontinuousphase
andwateristhecontinuousphasearetermedasoil-in-water
(o/w)emulsions.
•Suchemulsionsareusuallypreferredfororalusesincethe
disagreeabletasteandodouroftheoilisgenerallymasked
byemulsification.
•Additionally,theoilbeinginafinelydispersedstategets
easilyassimilatedinthebody.

3. •Emulsionsforintravenousadministrationshouldalsobeof
o/wtype.
•Oil-in-wateremulsionsarealsousefulforpreparationsfor
externalusesuchascreams,lotionsandlinimentssincethey
provideanon-greasyfeelingtotheproductandcaneasily
bewashedofffromtheskin.
2.Water-in-Oil Emulsions
•Water-in-oil(w/o)emulsionsarethoseinwhichoilforms
thecontinuousorexternalphasewhilewateristhe
dispersedordiscontinuousphase.
•Suchemulsionaremostlyusedexternallyascreamsand
lotions.
•Suchemulsionshaveanocclusiveeffectontheskinandare
usefulforthepreparationofmoisturizingcreams.

4. •Theyarealsousefulascleansingcreamssincethey
solubilizetheoil-solubledirtfromthesurface.
•Certainmedicamentssuchasantisepticsaremoreeffective
whenuseintheformofw/oemulsions.
•Theseemulsionsarehowevernotalwaysacceptable
cosmeticallybecauseoftheirgreasyfeeling.
3.MultipleEmulsions:
•Inadditiontothetwotypesofemulsionsdiscussedabove
therearecertaincomplex,multipleemulsionsinwhichthe
oil-in-waterorwater-in-oilemulsionsaredispersedin
anotherliquidmedium.

5. •Thus,anoil-in-water-in-oil(o/w/o)emulsionconsistsof
verysmalldropletsofoildispersedinthewaterglobulesof
awater-in-oilemulsionandawater-in-oil-in-water(w/o/w)
emulsionconsistsofdropletsofwaterdispersedintheoil
phaseofanoil-in-wateremulsion.
•Morecomplexsystemsuchaswater-in-oil-in-water-in-oil-
in-wateremulsions,havealsobeendeveloped.
•Thepreparationofmultipleemulsionsinvolvestwostages.
Forexample,aw/o/wemulsionispreparedbyfirstforming
awater-in-oilsystemandthendispersingthisprimary
emulsioninasecondaqueousphase.
•Multipleemulsionhavebeenproposedaspotential
candidatesforsustainedreleasedosageformssincethedrug
entrappedintheinnermostphasehastopassthroughtwo
otherphasesbeforebeingreleasedforabsorption.

6. 4.Micro emulsions:
•Normalemulsionsgenerallycontainglobulesrangingfrom
0.1to100mindiameter.
•Microemulsionsareemulsionsthatcontainglobuleshaving
diametersoflessthan0.1m.
•Dropletsofsuchdimensionscannotrefractlightand,asa
result,areinvisibletothenakedeye.
•Microemulsionsthereforeappearastransparentsolutions
andaremoreacceptablephysicallyincomparisonto
conventionalemulsions.
•Microemulsionshavebeenemployedforpreparationof
bothexternalaswellasinternalformulationswherethey
haveexhibitedbetterbioavailabilitythanconventional
emulsions.

7. Identification Of Emulsion Systems
•Anumberoftestshavebeenproposedtodeterminethetype
ofemulsion.However,theresultfromonetestshouldnotbe
takentobeconclusiveandtheidentityofanemulsiontype
shouldalwaysbeconfirmedbyatleasttwotestprocedures.
1.DilutionTest:
•Thetypeofemulsionmaybedeterminedbydilutingan
emulsionwithoilorwater.
•Anoil-in-wateremulsioncanbeeasilydilutedwithan
aqueoussolvent(e.g.,milk,ano/wemulsioncanbeeasily
dilutedwithwater)whereasawater-in-oilemulsioncanbe
dilutedwithaoilyliquid.
•Additionofthewrongliquidwillcausecrackingofthe
emulsion.

8. 2.Conductivity Test :
•Thistestisbasedontheprinciplethatanemulsionwithan
aqueouscontinuousphasewilltransmitanelectrical
currentwhereasonewithanoilycontinuousphasewill
not.
•Inthistest,apairofelectrodesconnectedtoalampandan
electricalsourceisgenerallydippedintoanemulsion.
•Iftheemulsioniso/wtype,thelampglows.
•Conductivitytests,however,maygivefalseresultswith
non-ionic oil-in-water emulsions.

9. 3.Dye Solubility Test:
•Whenawater-solubledyesuchasamaranthismixedwithan
emulsionandexaminedunderamicroscope,thecontinuous
phasewillappearcolourediftheemulsioniso/wtypewhilethe
globuleswillappearcolouredincaseofw/otype.
•Similarly,thecontinuousphaseofaw/oemulsionandthe
globulesofao/wemulsionwouldappearcolouredbyanoil-
solubledyesuchasSudanIII.
4.CobaltChlorideTest:
•Ifafilterpapersoakedinacobaltchloridesolutionandallowed
todryturnsfrombluetopinkonexposuretoanemulsion,it
indicatesthattheemulsionisoftheo/wtype.
•Thistesthowevermaynotworkiftheemulsionisunstableor
breaksinthepresenceofelectrolytes.

10. 5.Fluorescence Test:
•Ifadropofanemulsionisexposedtoultravioletradiation
andobservedunderamicroscopeawater-in-oilemulsion
shouldshowcontinuousfluorescencewhileanoil-in-water
typewouldshowonlyspottyfluorescence.
•Thisisbecausemanyoilshavethepropertytoexhibit
fluorescenceonexposuretoultravioletlight.
6.Direction of Creaming Test:
•Thedirectionofcreaminginanemulsioncanhelpinthe
identificationoftheemulsiontypeifthedensitiesofthe
aqueousandoilphasesareknown.
•Water-in-oilemulsionswouldnormallycreamdownwards
asoilisgenerallylessdensethanwater.Ontheotherhand,
o/wemulsionswouldnormallycreamupwards.

11. Pharmaceutical Applications of Emulsion
1.Emulsionscanbeusedtoadministerorallyunpleasanttasting
drugssuchasliquidparaffin,codliveroilandcastoroilina
palatableliquidformulation.
2.Oilsolubleaswellaswatersolublematerialscanbeformulated
intoasingledosageformasanemulsion.Forexample,oil
solublevitamins,A,DandEandwatersolubleonessuchas
vitaminsBandCcanbeformulatedasapalatablefine
emulsion.Suchaformulationalsoleadstobetterabsorptionof
vitamins.
3.Radio-opaqueemulsionsareusedfordiagnosticapplications
suchasX-rayexamination.
4.O/wtypeemulsionshavebeenusedforintravenous
administrationofoilsandfatswithhighcalorificvalueto
patientswhoareunabletoingestfoodbyoralroute.

12. 5.Emulsionsofbotho/wandw/otypeshaveextensively
beenusedtopreparepharmaceuticalpreparationsfor
externaluseandcosmeticpreparationssuchascreamsand
lotions.
6.Emulsificationhasalsobeenusedinaerosolproductsto
preparefoams.
7.Drugswhicharesusceptibletooxidationorhydrolysiscan
sometimesbestabilizedbyformulatingthemintheform
ofemulsion.
8.Bioavailabilityofcertainpoorlysolubledrugscanalsobe
improvedbydissolvingtheminoilandemulsifying.

13. Theories of Emulsification
•Whenoneliquidisbrokenintosmallparticles,theinterfacial
areaoftheglobulesconstitutesasurfacethatisenormous
comparedwiththesurfaceareaoftheoriginalliquid.
•Thereisanenormousincreaseinfreeenergyassociatedwith
thelargeincreaseinsurfaceareaoftheoilandhencesystem
becomesthermodynamicallyunstableandseparatesintotwo
phasesduetocoalescenceofoildroplets.
•Inordertostabilizetheemulsion,emulsifyingagentsare
added.Theseactbyreducingtheinterfacialtensionbetween
thetwophasesandformingastableinterfacialfilmbetween
thetwo.
•Thestabilityofapreparedemulsionisprimarilydetermined
bythestrengthandnatureoftheinterfacialfilmformed.

14. •Anidealemulsifyingagentforpharmaceuticaluseshould
bestable,inertandfreefromtoxicandirritantproperties.
•Itshouldpreferablybeodorless,tasteless,colorlessand
shouldproducestableemulsionsofthedesiredtypeatvery
lowconcentrations.
•Emulsifyingagentscanbebroadlyclassifiedintothree
groups:
1.Surfactantswhichgetadsorbedattheoil-waterinterfaceto
formmonomolecularfilmandtherebyreduceinterfacial
tension.
2.Hydrophiliccolloidswhichformamultimolecularfilmaround
thedisperseddropletsofoilinanoilinwateremulsion.
3.Finelydividedsolidswhichgetadsorbedattheinterface
betweenthetwoimmiscibleliquidphasesandformafilmof
particlesaroundthedispersedglobules.

15. EMULSIFYING AGENTS
•Emulsifyingagentsstabilizeemulsionsby
preventing/reducingthecoalescenceofdispersedglobules.
Thesepossesscertaindegreeofaffinitytopolarand
nonpolarliquids.Theyactasabridgebetweenthepolar
andnonpolarphasesandreducetheinterfacialtension.
Consequently,theemulsionisstabilized.
•Afewexamplesofemulsifyingagentsare:
Spans,Acacia,Soaps,Tweens,Gelatin
•Thoughemulsifyingagentshaveaffinitytowardspolarand
nonpolarliquids,theyhaveapreferentialsolubilityinone
oftheliquids.

16. •Surfactantismoresolubleinwatersousedino/w
emulsion.Forexampletweens,acacia,bentoniteareuseful
emulsifyingagentstoformo/wemulsions.
•Oilsolubleemulsifier,spansisemployedinthe
preparationofw/otypeofemulsion.
•Therelativesolubilityofanemulsifyingagentinoneof
thephasesisexpressedbyHLBscale,i.e.hydrophilic-
lipophilicbalance.

17. •Emulsifierswitha
highHLBvalue-solubleinwater-produceo/w
emulsions.ExamplesareTween80andsodiumoleate.
lowHLBvalue-oilsoluble-producew/oemulsions.
Examplesarespan80andglycerylmonostearate
•Combinationsofemulsifyingagents,i.e.oilsolubleand
thewatersoluble,impartbetterstabilitythanasingle
agent.
Forexample,ablendofTween20andSpan20willbe
suitableemulsifierforano/wemulsion.

18. EMULSIFYING AGENTS -MECHANISM OF ACTION
•A variety of emulsifying agents are used, each act by
different mechanisms.
•Irrespective of their chemical nature, they tend to
concentrate at the interface and form a tough film around
the globules.
•Based on the type of the films they form, emulsifying
agents are classified as:
•Surface active agents: soaps, spans, tweens
•Hydrophilic colloids: acacia, gelatin
•Finely divided solids: bentonite, veegum

19. Monomolecularadsorptionandfilmformation:
1.Surfactantsadsorbattheoil-waterinterfaceandforma
monomolecularfilm.Thisfilmrapidlyenvelopsthedroplets
assoonastheyareformed.Agentshavinghigherinterfacial
activityarebettersuitedforthispurpose.
•Themonomolecularfilmshouldbecompactandstrong
enoughsothatitcannotbeeasilydisturbedorbroken.For
anyreason,ifthefilmisbroken,itshouldbeelasticand
flexibleenough,sothatitcanbereformedrapidlyon
moderateagitation.
•Thephysical,chemicalandmechanicalpropertiesofthe
interfacialfilmsareofimportanceinstabilizingemulsions.
Attemptshavebeenmadetouseacombinationofsurfactants
ratherthanasingleonetoimpartthesecharacteristicstothe
interface.

20. •It is assumed that they support each other and strengthen
the monomolecular film. The surfactant blend consists of a
water soluble and an oil soluble surfactants.
•The hydrophilic surfactant approaches the interface from
aqueous phase side, while the oil-soluble surfactant
approaches from the oil phase-side. At the interface, the
two surfactants interact to form a complex and condense as
a monomolecular film.
•The interaction within a mixture of emulsifying agents at
the interface and nature of film formed is depicted in
figure.

21. EMULSIFYING AGENTS -MECHANISM OF ACTION
OIL
Sodium Cetylsulfate
Cholesterol
OIL
Sodium Cetylsulfate
Oleyl alcohol
OIL
Cetyl alcohol
Sodium Oleate
Excellent Emulsion
Poor Emulsion –loose
packing
Poor Emulsion –
negligible complexation

22. EMULSIFYING AGENTS -MECHANISM OF ACTION
•Acombinationofsodiumcetylsulfateandcholesterol
leadstoaclosepacked,complexfilmattheinterfacethat
producesanexcellentemulsion.Thusablendofsurface
activeagentsproducegoodemulsions.
•However,ablendofsurfactantsmayalsoproducepoor
qualityemulsion,iftheinteractionbetweenthemisnot
strongerattheinterface.Sodiumcetylsulfateandoleyl
alcoholdonotformaclosepackedfilmandtheir
combinationresultsinpooremulsion.
•Cetylalcoholandsodiumoleateproduceaclsoepacked
film,butcomplexationisnegligibleandagainproduce
pooremulsions.

23. 2.Surfactantsarecapableofreducingtheinterfacialtension.
Thisfacilitatestheimmediateformationofsmalldroplets.
Furthermore,itsimportancecanbeunderstoodby
consideringthesurfacefreeenergychangesduring
emulsification.
•Inequation,(Surfacefreeenergy)ΔG=γ
o/w.ΔA,ΔAis
increasedduetoformationofsmallglobules.Usually,these
smallglobulestendtocombinewitheachotherandform
separatephases.Butformationofsmallerdropletsis
importantinthepreparationofanemulsion.So,ΔAcannot
alteredtogetΔG=0.
•Theonlyoptionistoreducetheinterfacialtension,γ
o/w.
Surfactantsachievethisobjectiveandproducestable
emulsions.Thisfactorisofsecondaryimportancein
stabilization.

24. 3.Ionicsurfactantsimpartchargesoninterfacialfilms.These
filmsexertrepulsiveforcesbetweentwoapproaching
globulesandpreventtheircoalescence.
•Thismechanismisofimportance.Nonionicsurfactants
alsoproducegoodemulsions.
•Insuchcases,ionspresentintheaqueousphaseoftenget
adsorbedontothemonomolecularfilm,therebypreventing
thecoalescenceofdroplets.

25. Multimolecularadsorption:
•Theemulsifyingagentssuchasacaciaandgelatin,
(isoelectricpoint)tendtoformamultimolecularfilm
aroundtheglobulesandpreventscoalescence.
•Theyalsoreducetheinterfacialtensionmoderately,though
itisofsecondaryimportance.Theyareeffectiveathigh
concentrationandpromotetheformationofo/wemulsion
owingtotheirhydrophilicity.
•Theyalsohaveaffinitytowardstheoilphaseandthis
facilitatesinterfacialadsorption.Normally,thestabilityis
improvedbyaddingviscosityinducingagentssuchas
tragacanth,methylcellulose,CMCetc.

26. Solidparticleadsorption:
•Thefinelydividedsolidparticlesadsorbattheoil-water
interfaceandformarigidfilmofcloselypackedsolids.
Thisfilmactsasmechanicalbarrierandpreventsthe
coalescenceofglobules.Thesetendtoproducecoarse
emulsions.
•PowdersthatarewettedbywaterformO/Wemulsions,
whereasthosemoreeasilywettedbyoilformW/O
emulsions.
•Thestabilityofanemulsiondependsonthefinerstateof
solidparticles,irregularsurfaceandchargeonthesurface.

27. PHYSICAL INSTABILITY
•Emulsifyingagentshelptostabilizetheemulsion.Inspite
ofbestefforts,emulsionstendstobeunstable.
Flocculation:
•Inthiscase,neighboringglobulescomeclosertoeach
otherandformcoloniesintheexternalphase.
•Thisaggregationofglobulesisnotclearlyvisible.Thisis
probablytheinitialstagethatleadstoinstability.
•Theextentofflocculationofglobulesdependson
Globulesizedistribution
Chargeontheglobulesurface
Viscosityoftheexternalmedium

28. •Uniformsizeglobulespreventsflocculation.Thiscanbe
achievedbypropersizereductionprocess.
•Achargeontheglobulesexertrepulsiveforceswiththe
neighboringglobules.Thiscanbeachievedbyusingionic
emulsifyingagent,electrolytesetc.
•Iftheviscosityofexternalmediumisincreased,theglobules
becomerelativelyimmobileandflocculationcanbe
prevented.Thiscanbeobtainedbyaddingviscosity
improvingagentssuchashydrocolloidsorwaxes.
•Flocsslowlymoveeitherupwardsordownwardleadingto
creaming.Flocculationshouldnotbeconfusedwith
creaming.
•Flocculationisduetotheinteractionofattractiveand
repulsiveforces,whereascreamingisduetodensity
differenceinthetwophases.

29. Creaming:
•Creamingistheconcentrationofglobulesatthetopor
bottomoftheemulsion.Theflocculesmoveeitherupward
ordownwardleadingtocreaming.
•Creamingmayalsobeobservedonaccountofthe
movementofindividualglobules.Itcanbeobservedbya
differenceincolorshadeofthelayers.Itisareversible
process,i.ecreamcanberedispersedeasilybyagitation.
•Creamingisalsoconsideredtobethemarkofinstability.
•Increaming,thedrugisnotuniformlydistributed.This
leadstovariabledosage.Therefore,theemulsionshouldbe
shakenthoroughlybeforeuse.
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30. •Creamingisoftwotypes.Upwardcreaming,thisisdue
tothelessdenserinternalphase.Thisisobservedino/w
emulsion.Ontheotherhand,downwardcreamingis
alsopossibleiftheinternalphaseisheavier.Dueto
gravitationalpull,globulessettledown.Thisis
normallythecaseinw/oemulsions.
•Sincecreamingprocessinvolvesthemovementof
globulesinanemulsion,stokes’lawcanbeapplied.
•Therefore,creamingisinfluencedby:
Globulesize
Viscosityofthedispersionmedium
Differenceinthedensitiesofdispersedphaseand
dispersionmedium

31. Creaming can be reduced /prevented by:
•Reducing the particle size by homogenization.
•Increasing the viscosity of the external phase by
adding the thickening agents such as tragacanthor
sodium alginate.
•Reducing the difference in the densities between the
dispersed phase and dispersion medium. In general,
the density of aqueous phase is higher than the oil
phase. To make densities equal, oil soluble
substances such as β-bromonaphthalene,
bromoformare added to the oil phase. This
technique is rarely used in practice.
31

32. Coalescence :
•A few globules tend to fuse with each other and form
bigger globules. In this process, the emulsifier film
around the globules is destroyed to a certain extent.
•This step can be recognized by increased globule
size and reduced number of globules.
•Coalescence is followed by creaming stage.
•It is observed due to:
•Insufficient amount of the emulsifying agent
•Altered partitioning of the emulsifying agent
•Incompatibilities between emulsifying agents
32

33. •Phase volume ratio represents the relative volume of
water to oil in an emulsion.
•At higher ratio (>74% of oil to water), globules are
closely packed, wherein small globules occupy the
void spaces between bigger globules.
•Thus, globules get compressed and become irregular
in shape, which leads to fusion of adjacent globules.
33

34. Breaking:
•This is indicated by complete separation of oil and
aqueous phases.
•Creaming should be considered as separate from
breaking bcaz creaming is reversible process,
whereas breaking is an irreversible process.
•Cream floccules can be redispersed easily and a
uniform mixture is reconstituted by agitation bcaz the
oil globules are still surrounded by a protective
sheath of EA.
•When breaking occurs, simple mixing fails to
resuspend the globules into an uniform emulsion
bcaz the protective sheath around the globules is
completely destroyed.
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35. Phase Inversion:
•This involves the change of emulsion type from o/w
to w/o or vice versa.
•When we intend to prepare one type of emulsion say
o/w and if the final emulsion turns out to be w/o, it
can be termed as a sign of 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 % and by storing the emulsion in a
cool place.
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36. FACTORS WHICH IMPROVE PHYSICAL STABILITY
•Theories related to the stability of emulsions are
same as those mentioned in suspensions.
A.Particle size:
•As the globule size is reduced, they tend to exhibit
Brownian movement.
•According to stoke’slaw, the diameter of the globule
is considered as a major factor in creaming of
emulsions.
•The rate of creaming decreases four fold, when the
globule diameter is halved.
•It is necessary to choose the optimum globule size
for maximum stability.
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37. FACTORS WHICH IMPROVE PHYSICAL STABILITY
•On the industrial scale, emulsions are passed
through a colloid mill in order to achieve size
reduction of globules.
B.Particle size distribution:
•In general, globules of uniform size impart maximum
stability.
•In such emulsions, globules pack loosely and globule
to globule contact is less. However, it is difficult to
achieve a monodispersesystem due to a variety of
factors such as viscosity, phase volume ratio, density
of phases etc.
•Hence, an optimum degree of size dispersion range
should be chosen to achieve maximum physical
37

38. FACTORS WHICH IMPROVE PHYSICAL STABILITY
•If the size of globules are not uniform, globules of
smaller size occupy the spaces between the larger
globules. This type of closed packing induces greater
cohesion of globules which leads to coalescence.
C.Viscosity:
•As the viscosity increases, flocculation of globules
will be reduced because the mobility of globules is
restricted.
•Various thickening agents such as tragacanth,
veegum and cellulose derivatives are employed to
formulate emulsions for internal use.
•Long chain fatty acids and/or alcohols such as
beeswax, stearic acid, stearyl alcohol etc are used
when oil is the continuous phase in an emulsion.
38

39. FACTORS WHICH IMPROVE PHYSICAL STABILITY
D.Phase volume ratio:
•In an emulsion the relative volume of water and oil is
expressed as phase volume ratio.
•In general, most medical emulsions are prepared
with a volume ratio of 50:50.
•The upper limit 74% of oil can be incorporated in an
emulsion, but this may lead to breaking of the
emulsion. This value is referred to as critical point of
phase volume ratio.
•This critical point is defined as the concentration of
internal phase above which the emulsifying agent
can not produce a stable emulsion of the desired
type.
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40. FACTORS WHICH IMPROVE PHYSICAL STABILITY
•Beyond the critical point, the globules become
irregular in shape. The packing of globules is closest
leading to coalescence and defects in its morphology.
E.Charge of Electrical Double Layer:
•When ionic type of emulsifier is employed, the
electrical double layer possesses charge.
•The repulsive forces, due to like charge on the
globules, prevent the flocculation of globule.
•The charge on the electrical double layer also
depends on the pH of the preparation.
40

41. FACTORS WHICH IMPROVE PHYSICAL STABILITY
F.Physical properties of Interface:
•The interfacial film of the emulsifier is responsible for
enhancing the stability of the product.
•The film should be elasticenough to form rapidly as
soon as droplets are produced. This behavior
facilitates the production of emulsion.
•Similarly on moderate shaking, the emulsion should
be reconstituted. After manufacture, the film should
be tough so that coalescence of globules can be
prevented.
41

42. FACTORS WHICH IMPROVE PHYSICAL STABILITY
•Suitable emulsifying agents such as surfactants
should be selected to achieve the above film
properties at the interface.
•The physical properties of interface depends on the
pH of the preparation. Therefore, optimum pH has to
be maintained for maximum stability.
42

43. FACTORS WHICH IMPROVE PHYSICAL STABILITY
G.Densities of phases:
•It is not an usual practice to adjust the density of the
phases to the same value. Oil phase density can be
enhanced by adding brominated oil, when the oil is
an external phase.
H.Temperature fluctuations:
•Elevated temperatures alter the partition
characteristics of the emulsifiers and preservatives.
The net result is instability.
•Temperature also enhances the chemical
degradation of drugs and other ingredients.
•The chemical instability also leads to physical
instability.
43

44. FACTORS WHICH IMPROVE PHYSICAL STABILITY
•At lower temperature, the aqueous phase may
contain ice crystals, which rupture the interfacial film
and break the emulsion.
•Care should be taken to prevent temperature
fluctuations during manufacture and storage.
I.Poor experimental techniques:
•These lead to incomplete emulsification. Hence, the
process conditions including the sequence of steps
should be followed during manufacture.
•Besides, factors mentioned above, it is also important
to prevent the growth of microorganisms.
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45. Phase Inversion
•Phase inversion means a change of emulsion type
from o/w to w/o or vice versa. This technique is used
to prepare stable and fine emulsions.
•Phase inversion can be obtained by two ways.
(1)Changing the chemical nature of emulsifier:
•For instance, an o/w emulsion is prepared using
sodium stearate. Then calcium chloride is added to
form calcium stearate, which is oil soluble. Therefore,
oil phase becomes the continuous phase and w/o
emulsion is produced. Example is white liniment.
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46. Phase Inversion
(2) Altering the phase volume ratio:
•In this method, emulsifier is mixed with an oil and
then a small amount of water is added. Since the
volume of water is small compared to the oil, w/o
emulsion will be formed.
•As more water is added slowly, the inversion point is
gradually reached and the water as well as emulsifier
envelop the oil to small globules yielding an o/w
emulsion.
•If the method is not properly controlled, Phase
inversion can give a bad emulsion, which can cause
considerable difficulty in manufacture.46

47. Evaluation of Physical stability of emulsions
•Emulsions are evaluated for their chemical and
physical stabilities.
(a) Chemical stability study involves the study of
degradation of active drugs, emulsifiers,
preservatives, anti-oxidants etc. Chemical instability
also leads to physical instability.
(b) Physical stability study indicates the retaining of the
integrity of the dosage form during shelf life. An
emulsion is considered to be physically stable, if it
can restore its initial properties on moderate shaking.
47

48. Evaluation of Physical stability of emulsions
1. Extent of phase separation:
•The practical and commercial aspects of stability is
the study of phase separation.
•This is quick method and can be applied for poorly
formed and rapidly breaking emulsions.
•Separation of phases is visible after a definite period
of time, though the sign of instability begin quite
early.
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49. Evaluation of Physical stability of emulsions
2. Globule size distribution:
•An early sign of instability is indicated by the
appearance of bigger size globules. This is due to
aggregation and coalescence of small globules from
time to time, during storage.
•Therefore, microscopic examination of globule size
distribution analysis is an useful tool to evaluate the
physical stability.
49

50. Evaluation of Physical stability of emulsions
3. Accelerated stability studies-centrifugation
•Normally, flocculation and creaming are slow
processes. However, These processes can be
hastened by inducing stress conditions using
ultracentrifuge.
•The emulsions are subjected to different centrifugal
speeds at room temperature and the separation of
phases is observed at different time periods.
•A bad emulsion, normally, separates the oil instantly.
A good emulsion does not exhibit detectable
separation of oil phase, until certain time period, i.e.,
induction period. 50

51. Evaluation of Physical stability of emulsions
4. Microwave irradiation
The emulsion is exposed to microwave irradiation.
Then the surface temperature of the emulsion tends
to be highest and the temperature gradient between
the surface and the bottom of the emulsion must be
small for the most stable emulsion.
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52. Preservation of emulsions
•It is important that an emulsion should be free from
microbial contamination and growth.
•Microorganisms, such as fungi, bacteria and yeast,
use some of the ingredients of the emulsion for their
growth. As a result, these ingredients gets digested
leading to instability of the product.
•In case of parenteral emulsions, sterility of the
product is essential.
•Preservatives, such as, benzoic acid, sodium
benzoate, methyl paraben and propyl paraben, are
employed in the preparation of emulsions for non
parenteral use. Adequate concentration of these
preservatives has to be established.
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53. Preservation of emulsions
Some of the factors to be considered for the selection
of preservatives are:
•Type of emulsion
•volume fraction of aqueous phase
•pH of aqueous phase
•Binding of ingredients in the formulation
•Degree of aeration
•Type of container
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54. Preservation of emulsions
The optimum concentration of preservatives is
decided by considering the following features-
1. Aqueous phase:Bacteria are generally grown in the
aqueous phase, and at the oil-water interphase.
Therefore, the preservative should partition in favour
of the aqueous phase. Special care should be taken
on the use of preservative in o/w emulsions.
2. The volume fraction of the aqueous phase:The
higher the volume fraction of the aqueous phase, the
higher is the concentration of the preservatives
required. 54

55. Preservation of emulsions
3. pH of the aqueous phase:The preservative should
be in an undissociated form for its transport across
the membranes of the organism. The undissociated
form is effective as a bacteriostatic agent. The pH of
an aqueous phase should favour the formation of the
undissociated form.
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56. Rheologicproperties of Emulsions
•Emulsions are evaluated for its flow behavior.
•The following flow related attributes are desirable for
the overall performance of an emulsion:
(a) Removal of an emulsion from a bottle or tube.
(b) Flow of an emulsion through a hypodermic needle.
(c) Spreadibility of an emulsion on the skin.
(d) Stress induced flow changes during manufacture.
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57. Rheologicproperties of Emulsions
•In general, dilute emulsions exhibit Newtonian flow
and the comparison of flow curves among different
batches is easy.
•Analysis becomes complicated in case of
concentrated emulsions owing to their non-newtonian
flow.
•Multipoint viscometers such as cone and plate or cup
and bob type can be employed for evaluation.
•A rough guide regarding the type of flow can be
obtained based on phase volume ratio.
•An optimum level of viscosity is to be identified for
maximum physical stability.
57

58. Preparation of emulsion
•Before attempting to prepare an emulsion, it is
necessary to select the important components, viz.,
oil phase, and emulsifying agent.
Selection of oil phase:
A variety of substance have been used for oil phase.
A few examples are :
Fixed oil (corn, soya bean, peanut, sunflower oils)
Aliphatic hydrocarbons (liquid paraffin, turpentine oil
etc.)
Beeswax, spermaceti
Glycerides (long and medium chain)
Fatty acids and alcohols
58

59. Preparation of emulsion
•Many of them are prone to oxidation. Therefore, it is
necessary to include suitable antioxidant in the
formulation.
•Selection of oil phase is determined by several
factors.
(a)Desired physical properties of the product.
(b)Potential toxicity of the oil to the route of
administration,
(c)solubility of active product in the oil.
(d)Consistency of the product qualities.
(e) Any possible incompatibilities.
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60. Preparation of emulsion
•Based on these factors, the optimum volume of oil
should be selected. Generally, it is advisable to
prepare an emulsion containing less than about 25%
of dispersed phase in oil-in-water emulsion.
•Conversely, products containing a high percentage
(more than about 70 %) of dispersed phase exhibit
phase inversion. The phase volume ratio is also
applicable to water when it is used as dispersed
phase.
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61. Preparation of emulsion
Selection of Aqueous Phase:
Mostly water is used. Sometimes, the organoleptic
features of the emulsion demand the need of adding
sweeteners and flavoring agents. Sensitivity of skin
and nature of absorption determine the pH of
aqueous phase. In addition, electrolytes and
preservatives are included.
Based on the factors, optimum volume of aqueous
phase should be decided. Appropriate phase volume
ratio should be selected.
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62. Preparation of emulsion
Selection of an Emulsifying Agent:
•An emulsifying agent is selected depending on the
type of emulsion required.
•Selection of emulsifying agent is based on the
intended use. For internal use, non-ionic and water-
soluble emulsifying agents are chosen. For external
use, both ionic and non-ionic emulsifying agents are
employed.
•Another guiding principle is the Bancroft rule, which
suggest the nature of the emulsifying agent for each
emulsion.
•Furthermore, the principles of HLB scale can be
applied in its selection.
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63. Preparation of emulsion
•The required HLB value can be determined using
allegation method based on the nature of oil phase
and type of emulsion.
•It is essential to prepare a series of samples to study
the stability. Then optimum concentration of an
emulsifying agent should be obtained.
•It is better to avoid emulsifying agents obtained from
natural origin, because they show considerable batch
to batch variation. In addition, they also support the
microbial growth.
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64. Preparation of emulsion
•Wet Gum Method
•Dry Gum Method
•Small and large scale production
64