States of Matter 5.pdf unit 5 physical pharmaceutics 1

State of matter unit 5 pp

1. STATESOFMATTER
-Presentedby-
Ms.Poonam.D.Dighe
AmrutvahiniCollegeofPharmacy,Sangamner

2. EUTECTICS
INTRODUCTION
EUTECTICS:
Asubstancethatismeltedora substancethatisfused.
Amixtureofsubstanceshaving aminimummeltingpoint.
ThetermcomesfromtheGreek‘eutektos’,meaning‘easily
melted’
INTRODUCTION:
Physio-chemicalsystemscanbebedividedintotwotypes:
Homogeneous-eg:Sodiumchlorideinwater
Heterogeneous-eg:freezingwater

3. PHASE ANDCOMPONENT
PHASE:
Aphaseis definedasa homogeneousphysicallydistinct
andmechanicallyseparable portionofthesystem.
•EXAMPLE:FreezingWater.(homogeneous)
•Anexampleforheterogenousmixtureisgivenasfollows:
MgCo3(s)->MgO(s)+C02(g)
COMPONENT:
Thenumberofchemicalconstituentsthatmustbespecifiedinorder
to
describethecompositionofeachphase
present.EXAMPLE:CaCo3(s)-
>CaO(s)+CO2(g)

4. DEGREEOFFREEDOM
DEGREEOFFREEDOM:
•Itistheminimumnumberofindependentlyvariablefactors
phases
perfect
suchastemperature,pressure&compostionof
whichmustbearbitarilyspecifiedtorepresent
conditionofasystem.
•EXAMPLE:WATERhasnodegreeoffreedom.
SYSTEM:
•Anyportionoftheuniverseisolatedinan inertcontainer.

5. PHASERULE
Itstatesthatforaheterogeneoussysteminequilibriumnot
governedbyexternalforcessuchaselectricalandmagnetic
field,thenumberofdegreesoffreedom(F)isrelatedto
numberofcomponents(C)andnumberofphasesbythe
equation;
F=C-P+2

6. Two-ComponentSystemsContainingSolidand
LiquidPhases: EutecticMixtures
•solid–liquid mixtures in which the two components
are completely miscible in the liquid state and
completelyimmiscibleas solids.
•Examplesofsuchsystemsare:
•salol–thymol,
•salol–camphor,
•acetaminophen–propyphenazone.

7. Eutecticmixtureisdefinedasamixtureoftwoor
morecomponentswhichusuallydonotinteract
toformanewchemicalcompoundbut,whichat
certainratios,inhibitthecrystallizationprocess
ofoneanotherresultinginasystemhavinga
lowermeltingpointthaneitherofthe
components.
Eutecticmixtures,canbeformedbetweenActive
PharmaceuticalIngredients(APIs),between
APIsandexcipientorbetweenexcipient;thereby
providingavastscopeforitsapplicationsin
pharmaceuticalindustry.

8. SimpleEutecticSystems
Thegeneralform ofthephasediagramofsucha2-componentcondensedsystem
isshownin.HerethetwocomponentsAandBarecompletelymiscible in the
liquidstate,andthesesolutionsoncoolingyieldonlypureAorpureBas solid
phases.
Fig.SimpleEutecticDiagram

9. Thediagramconsistsof:
CurveAC;theFreezingpointcurveofA.ThepointArepresentsthe
freezingpointofA.ThecurveACshowsthatthefreezingpointofA
fallsbytheadditionofBtoA.Thusalongthiscurve,thesolidAisin
equilibriumwiththeliquidsolutionofBinA.
CurveBC;theFreezingpointcurveofB.ThepointBshowsthefreezing
pointofB.ThecurveBCexhibitsthefalloffreezingpointbythe
additionofAtoB.Alongthiscurve,thesolidBisinequilibriumwith
theliquidsolutionofAinB.
Applyingthereducedphaseruleequationtotheequilibriarepresented
bythecurveACandCB
i.e.,solidA/solutionandsolidB/solutionrespectively,wehave
F=C –P+1=2–2+ 1= 1
Thedegreeoffreedomis onei.e.,bothequilibriaaremonovariant

10. TheEutecticpointC.ThetwocurvesACandBCmeet atthepointC.Hereboththesolids
A and B must be in equilibrium with the solution phase (solution of A and B). The
numberofphasesis3. Byapplyingthereducedphaseruleequation,wehave
F'=C –P+1 =2–3+1=0
ThusthesystemrepresentedbythepointCisnonvariant.Inotherwords,boththe
temperatureandcompositionofthesystemsolidA/solidB/solutionarefixed.
ThemixtureofcomponentsAandBasatpointCmeltsatthelowest temperatureTE
indicatedon the graph.ThepointCistherefore,called theEutecticpoint(Greek
eutectos=easymelting). The
correspondingcomposition(CE)andtemperature(TE)areknown astheeutectic
compositionandtheeutectictemperaturerespectivelyofthesystem.
Theeutecticmixture,althoughithasadefinitemeltingpoint,isnottoberegardedas
acompound.Thereasonsare:(i) thecomponentsarenotinstoichiometric
proportions;and(ii)onexaminationunderamicroscopetheserevealtheexistence
ofseparatecrystalsofthecomponents.
TheAreaabovethecurvesACandBC.HerethetwocomponentsAandB arepresentas
liquid solutions of varying compositions. As a homogeneous solution of A and B
constitutesonephaseonly,thissystemisbivariant.
F=C–P+1 =2–1 +1 =2
Thereforetodefinethe systematany pointinthisarea, bothtemperatureand
compositionhavetobespecified.

11. Phase diagramforthethymol–salolsystemshowingthe
eutectic point.

12. Thymol–Salol system showing the
eutecticpoint
•therearefourregions:
•(i)asingleliquidphase.
•(ii)aregioncontainingsolidsaloland aconjugate
liquidphase.
•(iii) a region in which solid thymol is in equilibrium
withaconjugateliquidphase.
•(iv) a region in which both components are present
aspuresolidphases.

13. •Thoseregions containingtwophases(ii,iii, and iv)are
comparabletothetwo-phaseregionofthephenol–
watersystem.
•Thusitispossibletocalculateboththecompositionand
relativeamountofeachphasefromknowledge ofthetie
linesand thephaseboundaries.
•Assystemxisprogressivelycooled,moreandmoreof
thethymolseparates assolid.
•Assystemyiscooledthesolid phase thatseparatesat
22°Cispuresalol.

14. •Thelowesttemperatureatwhichaliquidphasecan
existinthesalol–thymolsystemis13°C,andthis
occursinamixturecontaining34%thymolinsalol.
•Thispointonthephasediagramisknownas
theeutecticpoint.
•Attheeutecticpoint,threephases(liquid,solidsalol,
andsolidthymol)coexist.

15. •Theeutecticpointdenotesaninvariantsystem
because,inacondensedsystem,
F= 2-3+ 1= 0.
•Theeutecticpointisthepointatwhichtheliquid
andsolidphaseshavethesamecomposition(the
eutecticcomposition).
intimatemixtureof
Thesolidphaseisan
finecrystalsofthetwo
compounds.
•Aeutecticoreutecticmixtureisamixtureoftwo
ormorephasesatacompositionthathasthe
lowestmeltingpoint.Theproperratiosofphases
toobtainaeutecticisidentifiedbytheeutectic
pointonabinaryphasediagram

16. DIFFERENCESBETWEENMELTINGPOINT,
EUTECTICPOINTANDTRIPLEPOINT
•1.MeltingPoint:Itisthetemperatureatwhichthesolid
andliquidphases,havingthesamecomposition,arein
equilibrium.SolidALiquidA.
•2.EutecticPoint:Itisthetemperatureatwhichtwosolidsand
aliquid phaseareinequilibriumSolidA+SolidBLiquid.
•3.TriplePoint:Itisthetemperatureatwhichthree
phasesarein equilibriumSolidLiquidVapour.

17. Eutecticmixtureformationisusually,
governedby followingfactors:
(a)Thecomponentsmustbemiscibleinliquidstate
andmostlyimmiscibleinsolidstate,
(b)Intimatecontactbetweeneutecticforming
materialsisnecessaryforcontactinducedmelting
pointdepression,
(c)Thecomponentsshouldhavechemicalgroups
thatcaninteracttoformphysicalbondssuchhas
intermolecularhydrogenbondingetc.,
(d)Themoleculeswhicharein
modifiedVantHoff’sequationcan
mixtures.
accordanceto
formeutectic

18. ApplicationsofEutecticMixturesin
PharmaceuticalIndustry
1.Duringpreformulationstage,
studiesbetweenAPIsandexcipient
roleinexcipientselection.
compatibility
playacrucial
2.Testingforeutecticmixtureformationcanhelpin
anticipationofprobablephysicalincompatibility
betweendrugandexcipientmolecules.
3.Eutecticmixturesarecommonlyusedindrug
designinganddeliveryprocessesforvariousroutes
ofadministration.

19. 4.Duringmanufacturingofpharmaceuticaldosageform,it
isextremelynecessarytoanticipatetheformationofeutectics
andavoidmanufacturingproblemsifany.Forexample,during
tabletcompactiontheheatproducedinthepunchanddie
cavitiesmayleadtofusionormeltingoftabletpowder
compactsleadingtomanufacturingdefects.Thusknowledge
ofeutecticpointsofpowdercomponentsmayhelpavoidthese
problems.
5.Duringpharmaceuticalanalysis,understandingofeutectic
mixturescanhelpintheidentificationofcompoundshaving
similarmeltingpoints.Compoundshavingsimilarmelting
points,asarulewillhavedifferenteutecticpointwitha
commonothercomponent.Thisknowledgecouldbeusedto
identifycompoundslikeErgotamine,Allobarbitaletc.The
listeddrugscanbedistinguishedbytheirtendencytoform
eutecticmixtureswithBenzanilide.

20. Someeutecticmixtures:
1.Curcumin-Nicotinamide(1:2)
2.Ibuprofen–Thymol(2:3)
3.Borneol–Menthol(1:9)
4.Urea–Acetaeninophen(1:17)
5.Ibuprofen–Menthol(1:9)