Solid state

Crystalline solids, Amorphous Solid

1. The SolidsState
Generalproperties
Crystalline Solids
Amorphous Solids
Meltingpoint

2. Generalproperties
Solidsaremuchdenserthanbothgasesandliquidsdueto
thepresenceofverystrongintermolecularforces.
Solidsareessentiallyincompressible(smallemptyspaces)
Solidshavedefinitevolumeandshape(rigid,notfluid)
Solidshaveno
translational
motion(only
vibration)

3. CrystallineSolids
Crystallinesolids,suchassodiumchloride,andmenthol,
arecomposedofstructuralunitsarrangedinfixed
geometricpatternsorlattices.
Menthol
SodiumChloride

4. CrystallineSolids
Crystallinesolidsshowdefinitemeltingpoints,passing
rathersharplyfromthesolidtotheliquidstate.
Themorphologyofacrystallineformisoftenreferredtoas
itshabit,wherethecrystalhabitisdefinedashavingthe
samestructurebutdifferentoutwardappearance.

5. CrystallineSolids
Types of crystallinesolids
The units that constitute the crystal structure can be atoms,
molecules, orions
.
IonicSolid
Latticeunitsconsistof
ionsheldtogetherby
ionicbondse.g.NaCl
AtomicSolid
Latticeunitsconsistof
atomsheldtogetherby
covalentbondse.g.
diamond
MolecularSolid
Latticeunitsconsistsof
moleculesheldtogether
byvanderWaalsforces
e.g.SolidCO
2
Ionic and atomic crystals in general are hard and brittle and have high melting
points, while molecular crystals are soft and have relatively low meltingpoints.

6. CrystallineSolids
Types of crystallinesolids
Metalliccrystalsarecomposedofpositivelychargedions
inafieldoffreelymovingelectrons.Theatomsareheld
togetherbymetallicbonding.
Metalsaregoodconductors
ofelectricitybecauseof
thefreemovementofthe
electronsinthelattice.
Metalsmaybesoftorhard
andhaveloworhigh
meltingpoints.

7. AmorphousSolids
Amorphoussolidsmaybeconsideredassupercooled
liquidsinwhichthemoleculesarearrangedina
somewhatrandommannerasintheliquidstate.
Amorphous Crystalline
Theydifferfromcrystallinesolidsinthattheytendtoflow
whensubjectedtosufficientpressureoveraperiodof
time,andtheydonothavedefinitemeltingpoints.

8. AmorphousSolids
Theamorphousstateisunstablecomparedtothe
crystallinesolid(ithashigherenergythancrystalline
solid).
Thepharmaceuticaladvantagesofamorphoussolidisits
highersolubilityandbioavailability.
Itspharmaceuticaldisadvantagesisitslowstability(over
time,amorphoussolidmaytransformtothemorestable
crystallinestate).

9. Meltingpoint
Heat offusion
Thetemperatureatwhichasolidpassesintoliquidstateis
knownasthemeltingpoint.Itisalsothefreezingpoint
oftheliquidstateofthatsolid.
Themeltingpointofapurecrystallinesolid(orfreezing
pointofaliquid)isthetemperatureatwhichthepure
liquidandsolidexistinequilibrium.
Normalmeltingorfreezingpointisthetemperatureofthe
equilibriummixtureatanexternalpressureof1atm.
Unliketheboilingpoint,themeltingpointisrelatively
insensitivetopressurebecausethesolid/liquidtransition
representsonlyasmallchangeinvolume.

10. Meltingpoint
Heat offusion
Theheat(energy)absorbedwhen1gofasolidmeltsorthe
heatliberatedwhenitfreezesisknownasthelatentheat
offusion.
∆?????? ????????????−????????????
=??????
∆?????? ∆????????????
V
landVs:themolarvolumes(cm
3/mole)oftheliquidandsolid,
respectively(Molarvolumeiscomputedbydividingthegram
molecularweightbythedensityofthecompound).
ΔH
f:themolarheatoffusion(theamountofheatabsorbedwhen1
moleofthesolidchangesintoliquid)
ΔT:thechangeofmeltingpointbroughtaboutbyapressurechange
ofΔP.

11. Meltingpoint
Intermolecularforces
•Theheatoffusionmaybeconsideredastheheat
requiredtoincreasetheinteratomicorintermolecular
distancesincrystals,thusallowingmelting(increased
molecularmotion)tooccur.
•Acrystalthatisboundtogetherbyweakforces
generallyhasalowheatoffusionandalowmelting
point,whereasoneboundtogetherbystrongforceshas
ahighheatoffusionandahighmeltingpoint.

12. Thermalanalysis
Applications
Thermal analysis has many applications in pharmaceutical
industry and quality control suchas:
Meltingpointsfororganicandinorganiccompoundsare
oftenusedforthermalanalysisfor-
Characterization and identification of compounds.
Determination of purity, polymorphism, and stability.
Investigation of drug compatibility withexcipient(s).

13. Thermal analysis
Definition
Thermalanalysisisanumberofmethodsforobserving
physicalandchemicalchanges(e.gmeltingpoint)ofa
materialuponheatingorcooling.
Themostcommontypesofthermalanalysisare:
Differntail scanning calorimetry(DSC)
Differential thermal analysis (DTA),
Thermogravimetric analysis (TGA)
Thermomechanical analysis(TMA).

14. Polymorphism
•Someelementslikecarbon(Dimond,graphite)and
sulphurexistinmorethanonecrystallineformwhichis
knownaspolymorphism
•Diamondismetastable(lessstable)formofcarbon
•Polymorphsexhibitdifferent-
•Meltingpoints
•Solubility
•Formationofdifferentpolymorphsdependupon
crystallizationconditions(Levelofsupersaturation,
temperature)

15. Pharmaceutical significance of
polymorphs
•Nearlyalllongchainorganiccompoundsexhibitpolymorphism
•Eg:Triglyceridetristearinshows
•Lowmeltingpointmetastable(α)
•Betaprime(β’)
•HighmeltingpointStablebeta(β)
•Theobroma(cocabutter)shows4formsγ,α,β’andβ.For
makingsuppositoriesTheobromashouldbemeltedatlowest
possibletemperature(33C)sothatstablepolymorph(βMP
34.5C))shouldnotdestroy.
•Becauseofdifferenceinsolubilitiesofpolymorphs,onemaybe
moreactivetherapeuticallythanother.E.g.Sulfameter
antimicrobialformIIismoreactivethanFormIII.
•Cortisoneacetatesuspension…outof5formsonlyoneisstable
inpresenceofwater.Duringpreparationofsuspensionstableform
shouldbeavailabletoavoidcaking.

16. References
Sinko,P.J.Martin'sphysicalpharmacyandpharmaceuticalsciences:
physicalchemicalandbiopharmaceuticalprinciplesinthe
pharmaceuticalsciences,Philadelphia,LippincottWilliams&
Wilkins.