药物晶型研究

药物的多晶型研究2024/1/28.提纲什么是晶体，多晶型？多晶型研究对药物开发的重要性如何筛选和选择药物的新晶型多晶型的主要分析手段晶型筛选实验的经验分享----溶剂选择2024/1/28.Crystal

Asolidmaterialwhoseconstituentatoms,molecules,orionsarearrangedinanorderlyrepeatingpatternextendinginallthreespatialdimensions.PharmaceuticalcrystalsMostdrugsaredevelopedascrystallineStabilityProcessabilityIPprotection什么是晶体？2024/1/28.什么是多晶型？Polymorphismistheabilityofasolidmaterialtoexistinmorethanoneformorcrystalstructure.PolymorphsSoldphaseSamechemicalcompositionDifferentmoleculararrangementsInpractice,weareinterestedinallthecrystallineandamorphousphasesforachemical/pharmaceutical2024/1/28.2024/1/28.多晶型研究对药物开发的重要性2024/1/28.药物多晶型研究的重要性2024/1/28.2024/1/28.2024/1/28.如何筛选和选择药物的新晶型.2024/1/28.2024/1/28.晶型的化学和物理分析手段2024/1/28.2024/1/28.2024/1/28.Experiencesharingonpolymorphscreening——solventselection2024/1/28.ThepurposeofpolymorphscreeningForInnovatorcompanies-selecttheoptimalsolid-stateofAPIfordevelopment-studyrelevantpolymorphsforIPprotectionForCROcompaniesbasedonthecustomersneeds-toidentifyasmanynewpolymorphs(includesolvate/hydrate)andamorphousformaspossible-ortofindthemoststableform

2024/1/28.Themethodofpolymorphscreeningcrystallizationcrystallizationfromsolution(slurry,anti-solventprecipitation,Solvent-thermalheating/coolingSlow/fastprecipitationfromsaturatedsolutions)recrystallizationfromaneatcompound(thermalheating/cooling,grinding,andhighpressure)2024/1/28.polymorphscreening——

crystallizationfromsolutiondegreeofsupersaturationandTemperatureareconsideredasthedrivingforceofcrystallisationdiversesolventsresultinthediscoveryofmorepolymorphs2024/1/28.crystallizationfromsolution——SolventselectionSlurryAnti-solventprecipitationSolvent-thermalheating/coolingexperimentsSlow/fastprecipitationfromsaturatedsolutionsmethodSolventVisualsolubility(mg/mL)MeOH

EtOH

IPA

1-Butanol

ACN

MEK

MIBK

EtOAc

iPrOAc

MTBE

2-MeTHF

DMF

NMP

DMSO

CH2Cl2

Toluene

1,4-Dioxane

Heptane

THF

Acetone

Water

2024/1/28.crystallizationfromsolution——

rationalexperimentaldesignLimitedresource

Howtofindasmanynewpolymorphsand

amorphousformaspossibleAPIpropertiesdifferentsolubilityinthesolvent

poorsolubilityorgoodsolubilitySolventproperties

Polarity-differentsortofsolvents(alcohols,ethers,esteretc.)BoilingpointFreezingpointToxicitymiscibility？2024/1/28.Slurry——solventselectionMakesurethesampleissuspension

solvent/mixedsolventssolubilityispoor2024/1/28.Anti-solventprecipitation

—solventselectionPreparesolventgoodsolubilityAnti-solventselectionPoorsolubilitypolaritymiscibility

miscibilityWaterDMFHeptaneACN1,4-DioxaneMTBEDMSO2024/1/28.Solvent-thermal

heating/coolingexperimentschangetemperaturesupersaturation

goodsolubilitySolventselectionsolubilityvarieswiththetemperature

freezingpointofthesolvent2024/1/28.Slow/fastprecipitationfromsaturatedsolutionsmethodEvaporatethesolventsupersaturationSlow/fastrateofcrystallization

SolventselectionlowboilingpointsolventboilingpointDMF152.8ºCDMSO189ºCNMP202ºC2024/1/28.Summary—Solven