Polymorphism in Pharmacy

Polymorphism is the ability of solid materials to exist in two or more crystalline forms with different arrangements or conformations of the constituents in the crystal lattice. ... More than 50% of active pharmaceutical ingredients (APIs) are estimated to have more than one polymorphic form

1. By-
Prof. Vedanshu Malviya
M.Pharm Pharmaceutics)
P.R. Pote Patil College of Pharmacy, Amravati-444604

2. CONTENTS
•Introduction
•Structuralaspectsofpolymorphism
•Propertiesofpolymorphism
•Typesofpolymorphism
•Conditionsresponsiblefordevelopmentofdifferent
polymorphicforms
•Methodsofpreparation
•Characterizationofpolymorphism
•Factorsaffectingpolymorphism
•Applications
•Conclusion
•References
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3. Introduction
•Theabilityofasubstancetooccurintwoormoredifferent
crystallineformswithadifferentialarrangementsand/or
conformationofthemoleculesinthecrystallatticeisknown
aspolymorphism
•Polymorphismisrelevanttothefieldsofpharmaceuticals,
agrochemicals,pigmentsandexplosives.
•Differencesintheinternalstructuresofpolymorphsresultsin
theirdistinctphysicalandchemicalproperties.
•Polymorphcontrolisimportantindrugdiscoveryand
developmentandalsoinrequiredbyregulatoryagencies.
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4. •Thephysicochemicalpropertiesofactivepharmaceutical
ingredientsarethekeyfactorsforthedevelopmentof
appropriatedosageforms.
•Allthephysicochemicalpropertiesinsolidstateareaffected
mainlyintermsofsolubility,dissolution,bioavailability,
processabilityandstability,itismandatorytoinvestigatethe
polymorphicbehaviorofactiveingredients.
•Theelementcarbonisthemostcommonexampleexhibiting
polymorphism.Itexistsintheformofgraphite(hexagonal),
diamond(cubic)andasfullerenes(C60,C70),andareshown
inFigNo.1.
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5. 5
© fullerenes
FigNo.1:PolymorphsofCarbon

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9. Difference between enantiotropy and monotropy
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Enantiotropy Monotropy
Reversiblephase transitionIrreversible phase transition
Metastable ↔ Stable Metastable → stable
Transition is endothermic Transition is exothermic
Lower melting form is
thermodynamically stable below
the transitiontemperature and
higher melting form is stable
above the transition temperature.
Highermelting form is always
thermodynamically stable form.
Lower meltingpointhas lower
heat offusion.
Highermelting point has high
heat of fusion.

10. Conditions responsible for the development of different
polymorphic forms
1.Solventeffects
2.Certainimpuritiesinhibitinggrowthpatternandfavorthe
growthofametastablepolymorphs.
3.Thelevelofsupersaturationfromwhichmaterialis
crystallized
4.Temperatureatwhichcrystallizationiscarriedout.
5.Geometryofcovalentbonds
6.Changeinstirringconditions.
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13. Factors affecting polymorphism
1.TemperatureandHumidity
•Storageconditionsaffectphysicochemicalreactionwhichare
acceleratedathighertemperature.
•Humidityactsasacatalystonthesolidsurface.
•E.g.Polymorphictransformationofcocoabutteroccursafter
heating.
2.Photostability
•Generallylightsensitivedrugareprotectedfromthe
photolyticdegradationbypackingthemsuitableinlight
resistantcontainer
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14. •Stablecrystallineformresistphotochemicaldegradationand
doesnotrequirelightresistantsystem.
•E.g.Acetametacin
3.Effectofsolvent
•Solventcanbringdramaticchangeingrowthmechanismand
morphology.
•Kineticofcrystalgrowingfromsolutionwasdeterminedby
twoimportantfactors.
1.Degreeofmolecularroughness
2.Natureofabsorptionofthesolventfromsurface.
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15. 4. Effect of grinding
•Grindingprocessreducesparticlesize,soincreasingspecific
surfaceareaandthatwhydirecteffectondissolutionrateand
bioavaibilityoftheformulation.
•Duringprocesssolidstatepolymorphictransformationonto
noncrystallineormetastableformiscausedbymechanical
action.
•E.g.Dihydrateformismorestablethananhydrousform.With
increasinggrindingtimecompoundbecomeunstablebecause
grindingweakenedbondingcrystalsandwatermolecules.
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16. 5.Effectoftabletcompression
•Stabilityandcompactionbehaviorformofthepolymorphic
formofdrugisimportant.
•E.g.Phenylbutazoneinwhichform3convertedtoform2at
˃2000kg/cm
2
.
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18. Conclusion
•Differencesinthesolubilityandmeltingpointmustbe
assessedandthenadecisioncanbemadetodeterminewhich
formtoprogressthroughtothenextstage
•Metastableformmayleadtopreferentialchoiceofa
polymorphotherthanstableform.
•Aspolymorphismcanhavesuchseriousconsequencesforthe
bioavailabilityofdrugswithlowaqueoussolubility.
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19. References
1.SharmaA,MishraR,TandonP.Polymorphismin
PharmaceuticalCompounds,AdvancementsandFuturistic
TrendsinMaterialScience,2011,40-48.
2.PrasanthiN.L,SudhirM,JyothiN,VajrapriyaV.Sri,A
ReviewonPolymorphismPerpetuates,AmericanJournalof
AdvancedDrugDelivery,2016,58-63.
3.RazaK,KumarP,RatanS,MalikR,AroraS,Polymorphism:
ThePhenomenonAffectingthePerformanceofDrugs,SOJ
PharmPharmSci,2014,1-10.
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20. 4.P.H.Karpinski,“Polymorphismofactivepharmaceutical
ingredients”Chem.Eng.Technol.,2006,vol.29(2),pp.233-237.
5.HarryG.Brittain,Polymorphisminpharmaceuticalsolids,
MarcelDekker,Inc,SpecialIndianedition,2008,pp.7-19.
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