4.2 Solubility of solids in liquids(0).ppt

FGJHKYIEH

1. Solubility of solids in liquids

2. Contents
Ideal and non ideal solubility
Solvation and association in polar solvents
Factors affecting solubility

3. Objectives of the lecture
After completion of this lecture, the student should
be able to:
Explain the ideal solution and real solution
Describe Solubility of strong and weak electrolytes

4. Ideal and non ideal solubility
Ideal solution
Thesolubilityofasolidinanidealsolutiondependson
Temperature
Meltingpointofthesolid
Molarheatoffusion∆H
f,(heatrequiredtomeltone
moleofsolidtoliquidwithoutchangingits
temperature)
Idealsolubilityisnotaffectedbythenatureofthe
solvent.

5. Ideal solution…
In an ideal solution
whereX’2isthemolfractionsolubilityinanideal
solution
ΔHfisthemolarheatoffusionofsolute
T0isthemeltingpointofsolute,andTisthesolution
temperaturesuchthatT<T0.
NB.itisassumedthatinanidealsolutiontheheatof
solutionisequaltotheheatoffusion

6. Ideal solution…
Example:whatisthesolubilityofnaphthaleneat
20
o
Cinanidealsolution?Themeltingpointof
naphthaleneis80
o
C,andthemolarheatoffusionis
4500cal/mole.
-logX
2
i
=∆H
f/2.303R(T
o-T)/TT
o
-logX
2
i
=4500 (353-293)
2.303x1.987293x353
X
2
i
=0.27

7. Non-ideal solutions
Heat of solution ≠Heat of fusion
the mole fraction solubility is the sum of two terms:
the solubility in an ideal solution +
the log of the activity coefficient of the solute
-log X’
2 = ΔH
fx T
o–T + log 
2.303 R T
oT
Theconventionalconcentrationtermsprovideacountof
molecules,atoms,orionsperunitvolumebutaffordno
indicationofthephysicalorchemicalactivityofthe
speciesmeasured,and
itisthisactivitythatdeterminesthephysicaland
chemicalpropertiesofthesystem

8. Activitymaybeconsideredlooselyasacorrected
concentrationorpressurethattakesintoaccountnot
onlythestoichiometricconcentrationorpressurebut
alsoany
intermolecularattractions
Repulsions
interactionsbetweensoluteandsolventinsolution
association,andionization
Thus,activitymeasurestheneteffectivenessofa
chemicalspecies.

9. Activity and Activity Coefficient
•The activity coefficient, γ
2, depending on the nature
of both the solute and solvent
•To account for non-ideality of solutions “activity” is used
instead of concentration in all equations
“Activity”:a
i= 
ic
i
Activity coefficient:
i
Log of activity co efficient considers
work of solubilization(overcome IMF)
Volume of solution
Total volume of solvent

11. Non-ideal solutions…
The total work as given by
(w
22+ w
11-2w
12)
The activity coefficient, γ
2, is to be proportional to
To the volume of the solute and
To the fraction of the total volume occupied by the
solvent.

12. Non-ideal solutions…
The log of the γ
2 is given by
logγ
2= [(w
11)
1/2
-(w
22)
1/2
]
2
V
2ф
1
2
2.303RT
In which
V
2is volume per mole of solute and
ф
1is the volume refraction, or X
1V
1/(X
1V
1+
X
2V
2) of the solvent,
R is the gas constant, 1.987 cal/mole degree
T is the absolute temperature of the solution.
 -logX
2= ∆H
f(T
o-T)+ V
2ф
1
2
(σ
1-σ
2)
2
2.303RT T
o 2.303RT

13. Non-ideal solutions…
Thewtermsrepresentingattractiveforces
Thetermsw11andw22areameasureoftheinternalenergy
orcohesiveforcesofthesolventandsolute,respectively.
w11istheamountofworkinvolvedinseparatingsolvent
moleculestocreatespaceforasolutemolecule
w22istheworkinvolvedinbreakingasolutemoleculefrom
itsbulk

14. Solvationand association in polar solvents
•Solvation
•Indissolutionofsoluteinsolventtheremaybe
stronginteractionssuchashydrogenbonding
•-vedeviation
•Association
•Whentheinteractionoccursb/nlikemoleculesof
oneofthecomponentsinasolution
•+vedeviation
•Example:dimerizationofbenzoicacidinsome
nonpolarsolventsortheinterlinkingofwater
moleculesbyhydrogenbonding

15. Factors affecting solubility
Temperature
Molecular structure
Nature of solvent and cosolvent
pH
Combined effect of solvent and pH
Common ion effect
Effect of indifferent electrolytes
Effect of complex formation
Effect of solubilizing agents

16. Temperature
Solubilityofstrongelectrolytes
•AriseinTwillincreasethesolubility
-endothermicprocess-95%ofsolutes
•AriseinTwilldecreasethesolubility
•exothermicdissolution
•TheseeffectconformstotheLeChatelier'sprinciple
–asystemtendstoadjustitselfinamannersoasto
counteractastresssuchasincreaseofT.

17. Solubility curve
Figure Effect of heat on solubility.

18. Solubility curve

19. Common ion effect
Solubilityofslightlysolubleelectrolyteisdescribedby
solubilityproduct,K
sp
ForsaturatedsolnofelectrolyteABinequilibriumwith
undissolvedsolid
AB
solid=A
+
+B
-
Accordingtolowofmassaction,theequilibrium
constantintermsofconc.isgivenby
K=[A+][B
-
]/[AB]

20. Common ion effect…
Sincetheconcentrationofthesolidphaseisessentially
constant,theeqnrewrittenas:
[A
+
][B
-
]=K
sp
IfanionincommonwithAB,(e.g.A+)isaddedtoa
solutionofAB,therewillbeamomentaryincreasein
ionicspecies:
[A
+
][B
-
]>K
sp
•Inordertore-establishtheequilibrium[A
+
][B
-
]=K
sp
SomeofABwillprecipitateout
Theadditioncompoundbearingthecommonion(e.g.,
AC)reducesthesolubilityofslightlysolublesalt
Example,Al(OH)
3andAgCl

21. Common ion effect…
AgCl
solid= Ag
+
+ Cl
-
Al(OH)
3solid= Al
3+
+ 3OH
-
K= [Ag+][Cl
-
] /[AgCl
solid] [Al
3+
][OH-]
3
= K
sp
K
sp=[Ag
+
][Cl
-
]
let us add NaCl into AgCl solution
Cl
-
ion increases
Momentarily [Ag
+
][Cl
-
] > K
sp
some of the AgCl precipitates from the solution until
the equilibrium [Ag
+
][Cl
-
] = K
spis reestablished.

22. pH (solubility of weak electrolytes)
Drugsmaybeclassifiedintothreecategoriesaccordingto
theirphysicalbehaviorinaqueoussolution:
strongelectrolytes-theymayexistentirelyasions,such
asK+,Cl−
Nonelectrolytes-theymaybeundissociated,aswiththe
steroidsandthesugars
weakelectrolytes-theymaybepartiallydissociated
andexistinbothanionicandamolecularform
Mostdrugsareweakacidsorbases&poorlysolublein
water.
Solubilityofweakelectrolytesisaffectedbychangein
pH

23. Weak acids
Solubilityofweakacids(itssalt)decreaseswith
decreaseinpH
Theproportionofunionizedmoleculesinsolution
increases(theyarelesssolublethanionized)
Example
Carboxylicacids(>5C)reacttoproducesolublesalt
withNaOH,carbonates&bicarbonates
Fattyacidsformsolublesoapwithalkalimetals
Alkalimetalsaltoftartaricacidissoluble
Phenolisweaklyacidic&Benzoicacidsaresoluble
inNaOHsolution
C
6H
6OH+NaOH=C
6H
5O-+H
2O

24. Weak bases
Solubilityofweakbases(itssalt)increaseswitha
decreaseinpH
Alkaloids, symphathomimetic amines,
antihistamines,localanestheticsandothers
Atropinesulfateandtetracainehydrochlorideare
formedbyreactingwithacids

25. Calculating the solubility of weak electrolytes as
influenced by PH
AtlowerpHtheionic&solublephenobarbitalsodium
isconvertedtolesssolublemolecularphenobarbital
thatprecipitates
Alkaloidalsaltssuchasatropinesulfatebeginsto
precipitateasthepHiselevated
Forhomogeneoussoln&maxtherapeuticeffect,the
preparetionshouldbeadjustedtooptimumpH.

26. pH…
At a certain pH, the relative conc. of the ionic and
the molecular moieties of a drug are given by the
Henderson-Hasselbalchequation.
For a weak acid HA, which ionizes according to
Equation
HA+H2O=H
3O
+
+ A−
the dissociation constant is given in Equation
Ka = [H
3O
+
] [A−]
[HA]
Ka = dissociation constant
A− = molar concentration of the acidic anion
H
3O
+
= molar concentration of the hydroniumion
HA = molar concentration of the undissociatedacid

27. pH…
thelogarithmofbothsides
pH=pKa+log[A-]/[HA]
Acidsaresubstancesdonatinghydrogenions,andbases
aresubstancesacceptinghydrogenions.
IftheacidBH+,whichisaconjugateofaweakbase
withahydrogenion,isincontactwithwater,an
ionizationordissociationconstantKacanbeobtained
fortheweakbase,too:
 BH
+
+H
2O=H
3O
+
+B
The Henderson-Hasselbalchequation for a weak base is
therefore as follows:
pH=pKa+log[B]/[BH+]

28. pH…
ThepHbelowwhichthesaltofaweakacid,
phenobarbitalsodium,forexample,beginsto
precipitatefromaqueoussolutionisreadilycalculated
inthefollowingmanner
Representingthefreeacidformofphenobarbitalas
HP&thesolubleionizedformasP-,equilibriumin
asaturatedsolnoftheslightlysolubleweak
electrolyteare
HP
solid=HP
sol
HP
sol+H
2O=H
3O
+
+P-

29. pH…
theequilibriunconstantisgiveninEquation
Ka=[H
3O
+
]+[P
−
]
[HP]
Thesolubilityofunionizedform:
So=HP
sol
Thetotal(theoverall)solubilitySofphbconsistsofthe
concoftheundissociatedacid[HP]&theconjugatebase
orionizedform[P−]:
S=[HP]+[P
−
]
ThepHbelowwhichthedrugseparatesfromsolutionas
theundissociatedacid,pH
p:
pHp= pKa+ log(S-So)/So

30. Example:BelowwhatpHwillfreephenobarbital
begintoseparatefromasolutionhavinganinitial
concentrationof1gofsodiumphenobarbitalper
100mLat25°C?Themolarsolubility,So,of
phenobarbitalis0.0050andthepKais7.41at
25°C.Themolecularweightofsodium
phenobarbitalis254.
Solution
Molarsolubility,S
o=0.0050mole/liter
Molarconc,S=10g/254=0.039mole/liter
pH
p=pKa+log(S-S
o)/S
o
=7.41+log(0.039-0.005)/0.005
=7.41+log(0.034/0.005)
=8.24

31. Combined effect of solvent and
pH
Addition of solvents such as alcohol to aqueous solution
may affect the solubility of weak electrolytes:
It increases the solubility of unionized species
It decreases the dissociation
Example:WhatistheminimumpHrequiredforthe
completesolubilityofthedruginsolutioncontaining
6gofphbNa(M.Wt:254)in100mlofa30%v/v
alcoholicsolution(givenpka&S
oofphbin30%v/v
alcohol=7.92&0.0276M),respectively)

32. Solution
Molarsolubility,S
o=0.0276mole/liter
Molarconc,S=60g/254=0.236mole/liter
pH
p=pKa+log(S-S
o)/S
o
=7.92+log(0.236-0.0276)/0.0276
=7.92+log(0.208/0.0276)
=7.92+0.877
=8.79

33. Effect of non-electrolytes on the solubility of
electrolytes
Thesolubilityofelectrolytesdependsonthedissociation
ofdissolvedmoleculesintoions.
Liquidswithahighdielectricconstant(e.g.water)are
abletoreducetheattractiveforces.
Ifawater-solublenon-electrolytesuchasalcoholisadded
toanaqueoussolutionofasparinglysolubleelectrolyte,
thesolubilityisdecreasedbecausethealcohollowers
thedielectricconstantofthesolventandionic
dissociationoftheelectrolytebecomesmoredifficult.

34. Effect of electrolytes on the solubility of non-electrolytes
Non-electrolytes
donotdissociateintoionsinaqueoussolution,
consistsofsinglemolecules.
Theirsolubilityinwaterdependsontheformationof
weakintermolecularbonds(hydrogenbonds)
Thepresenceofaverysolubleelectrolyte(e.g.
ammoniumsulphate),
theionsofwhichhaveamarkedaffinityforwater,
competingfortheaqueoussolvent&breakingthe
IMFbondsb/nthenon-electrolyteandthewater.

35. Effect of complex formation
InComplexformationtheapparentsolubilityofasolute
inaparticularliquidmaybe:
Increasesd
Thesolubilityofmercuriciodide(HgI
2)becauseof
theformationofawatersolublecomplex,K
2(HgI
4)
Cyclodextrineincreasessolubility
Decreased
TTCformaninsolublecomplexwithcalciumions

36. Effects of Solubilizingagents
Theseagentsformlargeaggregatesormicellesin
solution>CMC
Inaqueoussolutionthecentreoftheseaggregates
resemblesaseparateorganicphase
Solubilityoforganicsolutesisincreasesastheymaybe
takenupbytheaggregates
Inorganicsolventsthecentreoftheaggregatesinthese
systemsconstitutesamorepolarregion
Solubilityofpolarsolutesincreasesastheyaretaken
upintotheseregions

37. Distribution Phenomena
Ifliquidorsolidisaddedtoamixtureoftwo
immiscibleliquids,itwillbecomedistributedbetween
thetwolayersinadefiniteconcentrationratio.
IfC1andC2aretheequilibriumconcentrationsofthe
substanceinSolvent1andSolvent2,respectively,the
equilibriumexpressionbecomes
C1/C2=K
The equilibrium constant, K, is known as the
distribution ratio,
distribution coefficient, or partition coefficient

38. Example Distribution Coefficient
Whenboricacidisdistributedbetweenwaterand
amylalcoholat25°C,theconcentrationinwateris
foundtobe0.0510mole/literandinamylalcoholitis
foundtobe0.0155mole/liter.Whatisthedistribution
coefficient?
Noconventionhasbeenestablishedwithregardto
whethertheconcentrationinthewaterphaseorthat
intheorganicphaseshouldbeplacedinthe
numerator.Therefore,theresultcanalsobe
expressedas
Oneshouldalwaysspecify,whichofthesetwoways
thedistributionconstantisbeingexpressed

39. Partition coefficient (P)
Partitioncoefficient(P)isaparameterthat
characterizetherelativeaffinityofcompoundin
itsunionizedformforwaterandanimmisibile
modellipidsolvent(octanol)
Octanolwaschosenasmodellipidphase
becauseitmostcloselysimulatesthe
propertiesofbiologicalmembranes
Partitioncoefficientcanbemeasured
experimentally
bydissolvingaknownamountofdruginwater,
mixingthesolutionwellwithoctanoland
allowingenoughtimeforthemixturetoreach
equilibriuminpartitioningbetweenthetwo

40. Partition coefficient (P) Interpretation
P>1orlogP>0impliesthatthedrughas
affinityforlipidmembrane
P<1orlogP<0impliesthatthedrughas
affinityforwaterorhydrophiliclayer.
LogPprovidesthepharmacistanappreciation
ofthedrug'spartitioningpreference.
ApositivelogPtellsusthatmoredrughas
movedintooctanol
AnegativelogPtellsusthatthedrughas
partitionedmoreintowater.
AlogPof2indicatesthatthereare100
moleculesofdruginoctanolforevery1
moleculeofdruginthewaterphase

41. Effect of Ionic Dissociation & Molecular Association on Partition
Whenassociationanddissociationofdrugoccur,
thesituationbecomesmorecomplicated.
E.g.benzoicacidassociatesintheoilphaseand
dissociatesintheaqueousphase
Drugsthatareweakacidsorweakbasesionizein
waterdependingonpKaandpHoftheaqueous
phase
Ingeneral,ionizedstructurecannotpartitionin
octanolorotherhydrophobicsolvent
Pvaluecannotbeusedtoassessthetrue
distributionofionizabledrugintwoimmiscible
phase
Becauseitsvalueisdependentontheionicstate
ofthedrug(whichinturndependsonpH)

42. Apparent distribution coefficient
P = Co/Cw
Co = [HA]o

43. Pharmaceutical Application
Knowledgeofpartitionisimportanttothepharmacist
becausetheprincipleisinvolvedinseveralareasof
currentpharmaceuticalinterest.Theseinclude
1.preservationofoil–watersystems
2.theabsorptionanddistributionofdrugsthroughout
thebody
3.Extractionofactiveingredientsfromcrudedrug

44. Extraction
Partitioncoefficientisusedtodeterminethe
efficiencywithwhichonesolventcanextracta
compoundfromasecondsolvent.
Supposethatwgramsofasoluteisextracted
repeatedlyfromV1mLofonesolventwith
successiveportionsofV2mLofasecondsolvent,
whichisimmisciblewiththefirst
Letw1betheweightofthesoluteremaininginthe
originalsolventafterextractingwiththefirstportion
oftheothersolvent
Then,theconcentrationofsoluteremaininginthe
firstsolventis(w1/V1)g/mLandtheconcentration
ofthesoluteintheextractingsolventis(w-w1)/V2
g/mL.

45. The process can be repeated, and after n extractions
The distribution coefficient is thus
Byuseofthisequation,itcanbeshownthatmost
efficientextractionresultswhennislargeandV2issmall
inotherwords,whenalargenumberofextractionsare
carriedoutwithsmallportionsofextractingliquid

46. Example Distribution Coefficient
Thedistributioncoefficientforiodinebetweenwater
andcarbontetrachlorideat25°CisK=CH2O/CCCl4
=0.012.Howmanygramsofiodineareextracted
fromasolutioninwatercontaining0.1gin50mLby
oneextractionwith10mLofCCl4?Howmany
gramsareextractedbytwo5-mLportionsofCCl4?
Thus, 0.0011 g of iodine remains in the water phase,
and the two portions of CCl4 have extracted 0.0989
g.