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).

(ontinuous phase Dispersed phase

2o stabili e these droplets, emulsif#ing agent should be added

Microemulsion: Droplets si e range !.!" to !." m Macroemulsion: Droplets si e range approximatel# $ m. General Types of Pharmaceutical Emulsions: ") %otions &) %iniments ') (reams )) *intments $) +itamin drops Primary and secondary emulsion: ,rimar# emulsion containing one internal phase, for example, oil-inwater emulsion (o.w) and water-in-oil emulsion (w.o). /econdar# emulsion= multiple-emulsion: it contains two internal phase, for instance, o.w.o or w.o.w. 0t can be used to dela# release or *il to increase the stabilit# of the acti1e compounds. 3ater
*il 3ater

O/W

W/O

3ater *il *il 3ater

*il 3ater

O/W/O

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W/O/W

Emulsion Type and Means of Detection: using of na4ed e#e, it is 1er# difficult to differentiate between o.w or w.o emulsions. 2hus, the four following methods ha1e been used to identif# the t#pe if emulsions. 1) Dilution Test: based on the solubilit# of external phase of emulsion. - o.w emulsion can be diluted with water. - w.o emulsion can be diluted with oil.
8ew drops of water 3ater distribute uniforml# *.3 emulsion

8ew drops of emulsion

3ater separate out as la#er

3.* emulsion

&) Conducti ity Test: water is good conductor of electricit# whereas oil is non-conductor. 2herefore, continuous phase of water runs electricit# more than continuous phase of oil.
6ulb

5lectrode 5mulsion

= 6ulb glows with *.3 = 6ulb doesn7t glow with 3.*

') Dye!"olu#ility Test: - 3ater-soluble d#e will dissol1e in the aqueous phase. - *il-soluble d#e will dissol1e in the oil phase.

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3hat is loo4 li4e under the microscope after mixing with suitable d#e

*il-soluble d#e (e.g. /carlet)

3ater-soluble d#e (e.g. Amaranth d#e)

3.*

*.3

*.3

3.*

$!%luorescence test: oils gi1e fluorescence under 9+ light, while water doesn7t. 2herefore, *.3 emulsion shows spott# pattern while 3.* emulsion fluoresces.

,harmaceutical applications of emulsions:

". 2o mas4 the taste &. *.3 is con1enient means of orall# administration of water-insoluble liquids '. *.3 emulsion facilitates the absorption of water-insoluble compounds comparing to their oil# solution preparations (e.g. 1itamins) ). *il-soluble drugs can be gi1en parentrall# in form of oil-in water emulsion. (e.g 2axol) $. 5mulsion can be used for external application in cosmetic and therapeutic uses.

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Theories of Emulsification:

0ncase of two immiscible liquids

*il *il 3ater Agitation 3ater *il 3ater

/eparate rapidl# into two clear defined la#ers

An explanation of this phenomenon is because of cohesi1e force between the molecules of each separate liquid exceeds adhesi1e force between two liquids. 2his is manifested as interfacial energ# or tension at boundar# between the liquids.
/mall droplet /urface area 0nterfacial tension /#stem is thermod#namicall# unstable : high energ#; /#stem tends to separate in two la#er to reduce the surface area

2herefore, to pre1ent the coalescence and separation, emulsif#ing agents ha1e been used. 2#pes of emulsif#ing agents: ". /urface acti1e agent: adsorbed at oil.water interface to form monomolecular film to reduce the interfacial tension

&. <#drophilic colloids: forming a multimolecular film around the dispersed droplet '. 8inel# di1ided solid particles: the# are adsorbed at the interface between two immiscible liquid phases to form particulate film

&!Monomolecular adsorption

3= . A /
/urface area /urface free energ# 0nterfacial tension

0n emulsion, the surface area is high to maintain the dispersion of the droplets. 2hus, based on the abo1e equation surface free energ# becomes high consequentl#. 2he onl# wa# to 4eep it low is to reduce the interfacial tension. /urface acti1e agent (/AA) is molecule which ha1e two parts, one is h#drophilic and the other is h#drophobic. 9pon the addition of /AA, the# tend to form monola#er film at the oil.water interface.
<#drophilic head <#drophobic tail

3ater
8orm monomolecular film

*il
2he functions of surface acti1e agents to pro1ide stabilit# to dispersed droplets are as following: i. =eduction of the interfacial tension

ii. 8orm coherent monola#er to pre1ent the coalescence of two droplet when the# approach each other iii. ,ro1ide surface charge which cause repulsion between ad>ust particles (ombination of surface-acti1e agents is used most frequentl#. 2he combination should form film that closel# pac4ed and condensed

2his figures shows schematic of oil droplets in an oilwater emulsion. @ou can see the orientation of a 2ween and a /pan molecule at the interface

8igure (a) shows good combination, which forms excellent emulsion. 8igure (b) and (c) show poor emulsion due to lac4 of closel# pac4ed or lac4 of complexation, ? respecti1el#.

(lassification of surface-acti1e agents:

Bote that: Anionic /AA are mainl# used for external used. (ationic /AA are used for external used. 2he# ha1e, also, good antimicrobial acti1it# (e.g. 6en al4onium chloride) Bonionic /AA are stable o1er wide range of p<. 2he# are not affected b# change in p< or addition of electrol#tes. 2he# are less toxic and main function to pro1ide steric repulsion

'!Multimolecular adsorption
,ol#saccharides Amphoterics /#nthetic or semi-s#nthetic pol#mers (arbomer resins (ellulose ethers (arbox#meth#l chitin ,5D-n (eth#lene oxide pol#mer)

Acacia Agar Alginic acid (arrageenan Duar gum Earra#a gum 2ragacanth

Delatin

<#drophilic colloids form multimolecular adsorption at the oil. water interface. 2he# ha1e low effect on the surface tension. 2heir main function as emulsion stabili ers is b# ma4ing coherent multi-molecular film. 2his film is strong and resists the coalescence. 2he# ha1e, also, an auxiliar# effect b# increasing the 1iscosit# of dispersion medium. Most of the h#drophilic colloids form oil-in-water emulsions. /ome of them can pro1ide electrostatic repulsion li4e acacia, which contains Arabic acid and proteins ((**< and B<')

colloids

C!"olid particle adsorption 8inel# di1ided solid particles are adsorbed at the surface of emulsion droplet to stabili e them. 2hose particles are wetted b# both oil and water (but not dissol1ed) and the concentration of these particles form a particulate film that pre1ent the coalescence.

,articles that are wetted preferentiall# b# water from o.w emulsion, whereas those wetted more b# oil form w.o emulsion Bote that the# are 1er# rare to use and can affect rheolog# of the final product /i e of the particle is 1er# important, larger particles can lead to coalescence

8inel# di1ided solids

6entonite <ectorite Eaolin Magnesium aluminum silicate Montmorillonite Aluminum h#droxide Magesium h#droxide /ilica

Other emulsifyin( a(ents Batural emulsif#ing agents: ". 5gg #ol4: it contains phospholipids and cholesterol. 2he main withdraw bac4 is that spoils quic4l#G therefore, it can7t be used in industr#. 0t is used for extemporaneous preparation. &. 3ool fat: anh#drous lanolin, it is used to prepare w.o emulsion for external uses. '. /tarch: it forms starch mucilage and it is restricted for enemas preparation. ). (holesterol: it has stabili ing actionG therefore, another emulsifier should be included. )o* to control emulsion type durin( formulation+ a. +olume of internal and external phases controls the t#pe of emulsion. 2he smaller 1olume will be for the internal phase and the larger 1olume will be for external phase. 0n some cases, internal phases can be more than $!H of the total 1olume (see the following section) b. Dominance of polar and non-polar characteristic of emulsif#ing agents (relati1e solubilit# of emulsif#ing 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. Bote that polar groups are better barriers than non-polarG therefore, o.w emulsion can be prepared with more than $! H of oil phase : internal phase;. What the factors that affect the choice of emulsion type+ 2he choice of emulsion depends on (")-properties and uses of final products (&)- the other material required to be present. *il-soluble drug is prepared in o.w emulsion due its solubilit# and its taste can be mas4ed b# adding fla1oring agents 8or intra1enous in>ection : i.1.; o.w emulsion is the onl# t#pe could be used.
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8or intramuscular in>ection :i.m.; both o.w and w.o t#pes of emulsion could be used. 3ater-soluble drug can be prepared in w.o emulsion to get prolonged action (depot therap#)

2opical application: o /emisolid emulsions are called creams and lotions Oil in water emulsion
8or insoluble drug 8or local effect 5asil# to wash from s4in Doesn7t ha1e greas# texture of oil# preparation Acceptable b# consumer

Water in oil emulsion

8or water soluble drug (an be use to h#drate the upper la#er of stratum corneum (moisturi ing cream) (an increase the absorption of drug from these formulation (an be used to clean s4in from dirt Bot acceptable b# consumer

Methods for preparation of emulsion:

0n small scales such as in pharmac#-hospital labs, mortar and pestle are the needed equipments. 0n large scale such as in pharmaceutical industr#, different machines are used:
1, Mixer or mechanical stirring: the emulsion is prepared b#

agitation of emulsion ingredient

-,

(olloid mills

.,

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5mulsif#ing Agents: ") (arboh#drate Materials: Acacia, 2ragacanth, Agar, ,ectin. o.w emulsion. &) ,rotein /ubstances: Delatin, 5gg #ol4, (aesin o.w emulsion. ') <igh Molecular 3eight Alcohols: /tear#l Alcohol, (et#l Alcohol, Dl#cer#l Mono stearate-----------o.w emulsion. cholesterol------------------------------------------------------- w.o emulsion )) 3etting Agents: Anionic, (ationic, Bonionic o.w emulsion w.o emulsion $) 8inel# di1ided solids: 6entonite, Magnesium <#droxide, Aluminum <#droxide o.w emulsion. Phase /n ersion: 2he relati1e 1olume of internal and external phases of an emulsion is important. (increase) internal concentration (increase) 1iscosit# up to a certain point. +iscosit# will decrease after that point. At this point the emulsion has undergone in1ersion i.e. it has changed from an o.w to a w.o, or 1ice 1ersa. 0n practice, emulsions ma# be prepared without in1ersion with as much as about A$H of the 1ol. of the product being internal phase.

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Methods of Preparation of Emulsions: ") (ontinental or Dr# Dum Method: I):&:"I Method ) parts (1olumes) of oil JAnsel. Ath ed. page '?FK & parts of water " part of gum Acacia or other o.w emulsifier is triturated with oil in a perfectl# dr# 3edgwood or porcelain mortar until thoroughl# mixed. Dlass mortar has too smooth a surface to produce the proper si e reduction of the internal phase (Do not use glass mortar). After the oil and gum ha1e been mixed, the two parts of water are then added all at once and the mixture is triturated immediatel#. &) 5nglish or wet Dum Method: /ame proportion of oil, water and gum are used as in the continental or dr# gum method but the order of mixing is different. Mucilage of the gum is prepared b# triturating acacia (or other emulsifier) with water. 2he oil is then added slowl# in portions, and the mixture is triturated to emulsif# the oil. /hould the mixture become too thic4 during the process, additional water ma# be blended into the mixture before another successi1e portion of oil is added. ') 6ottle or 8orbes 6ottle Method: 9seful for5xtemporaneous preparation of emulsion from 1olatile oils or oleaginous substance of low 1iscosit#. put powdered acacia in a dr# bottle Add & parts of oil

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2horoughl# sha4e the mixture in the capped bottle. A 1olume of water approximatel# equal to the oil is then added in portions, the mixture being thoroughl# sha4en after each addition. 2his method is not suitable for 1iscous oils (i.e. high 1iscosit# oil). "ta#ility of Emulsion: An emulsion is considered to be ph#sicall# unstable if : a) 2he internal phase tends to form aggregates of globules. b) %arge globules or aggregates of globules rise to the top or fall to the bottom of the emulsion to form a concentrated la#er of the internal phase. c) 0f all or part of the liquid of the internal phase becomes Iunemulsified on the top or bottom of the emulsion. /eparation of the internal phase from the external phase is called 6=5AE0BD of the emulsion. 2his is irre1ersible. -,rotect emulsions against the extremes of cold and heat. -5mulsions ma# be ad1ersel# affected b# microbial contamination. Dels and Magmas: Dels are defined as semisolid s#stems consisting of dispersions made up of either small inorganic particles or large organic molecules enclosing or interpenetrated b# a liquid. Magmas or Mil4s are gels consisted of floccules of small distinct particles. Dels and Magmas are considered colloids because the# contain particles within the range of colloidal dispersions. 5xamples of Magmas L Dels: 6entonite Magma, B8: ,reparation of $H bentonite, a nati1e, colloidal h#drated aluminum silicate, in purified water. Aluminum <#droxide Del, 9/,:

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2his is an aqueous suspension of a gelatinous precipitate composed of insoluble aluminum h#droxide and h#drated aluminum oxide, equi1alent to about )H of aluminum oxide. Mil4 of Magnesia, 9/,: 2his is a preparation containing between A and C.$H of Magnesium h#droxide.

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