药物晶型研究演示

（优选）药物晶型研究目前一页\总数二十五页\编于十九点2023/5/15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----溶剂选择目前二页\总数二十五页\编于十九点2023/5/15Crystal

Asolidmaterialwhoseconstituentatoms,molecules,orionsarearrangedinanorderlyrepeatingpatternextendinginallthreespatialdimensions.PharmaceuticalcrystalsMostdrugsaredevelopedascrystallineStabilityProcessabilityIPprotection什么是晶体？目前三页\总数二十五页\编于十九点什么是多晶型？

Polymorphismistheabilityofasolidmaterialtoexistinmorethanoneformorcrystalstructure.PolymorphsSoldphaseSamechemicalcompositionDifferentmoleculararrangementsInpractice,weareinterestedinallthecrystallineandamorphousphasesforachemical/pharmaceutical2023/5/15目前四页\总数二十五页\编于十九点2023/5/15目前五页\总数二十五页\编于十九点2023/5/15多晶型研究对药物开发的重要性目前六页\总数二十五页\编于十九点2023/5/15药物多晶型研究的重要性目前七页\总数二十五页\编于十九点2023/5/15目前八页\总数二十五页\编于十九点2023/5/15目前九页\总数二十五页\编于十九点如何筛选和选择药物的新晶型目前十页\总数二十五页\编于十九点2023/5/15目前十一页\总数二十五页\编于十九点2023/5/15目前十二页\总数二十五页\编于十九点2023/5/15晶型的化学和物理分析手段目前十三页\总数二十五页\编于十九点2023/5/15目前十四页\总数二十五页\编于十九点2023/5/15目前十五页\总数二十五页\编于十九点2023/5/15Experiencesharingonpolymorphscreening——solventselection目前十六页\总数二十五页\编于十九点2023/5/15ThepurposeofpolymorphscreeningForInnovatorcompanies-selecttheoptimalsolid-stateofAPIfordevelopment-studyrelevantpolymorphsforIPprotectionForCROcompaniesbasedonthecustomersneeds-toidentifyasmanynewpolymorphs(includesolvate/hydrate)andamorphousformaspossible-ortofindthemoststableform

目前十七页\总数二十五页\编于十九点Themethodofpolymorphscreening2023/5/15crystallizationcrystallizationfromsolution(slurry,anti-solventprecipitation,Solvent-thermalheating/coolingSlow/fastprecipitationfromsaturatedsolutions)recrystallizationfromaneatcompound(thermalheating/cooling,grinding,andhighpressure)目前十八页\总数二十五页\编于十九点polymorphscreening——

crystallizationfromsolution2023/5/15degreeofsupersaturationandTemperatureareconsideredasthedrivingforceofcrystallisationdiversesolventsresultinthediscoveryofmorepolymorphs目前十九页\总数二十五页\编于十九点crystallizationfromsolution——Solventselection2023/5/15SlurryAnti-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

目前二十页\总数二十五页\编于十九点crystallizationfromsolution——

rationalexperimentaldesign2023/5/15Limitedresource

Howtofindasmanynewpolymorphsand

amorphousformaspossibleAPIpropertiesdifferentsolubilityinthesolvent

poorsolubilityorgoodsolubilitySolventproperties

Polarity-differentsortofsolvents(alcohols,ethers,esteretc.)BoilingpointFreezingpointToxicitymiscibility？目前二十一页\总数二十五页\编于十九点2023/5/15Slurry——solventselectionMakesurethesampleissuspension

solvent/mixedsolventssolubilityispoor目前二十二页\总数二十五页\编于十九点2023/5/15Anti-solventprecipitation

—solventselectionPreparesolventgoodsolubilityAnti-solventselectionPoorsolubilitypolaritymiscibility

miscibilityWaterDMFHeptaneACN1,4-DioxaneMTBEDMSO目前二十三页\总数二十五页\编于十九点Solvent-thermal

heating/coolingexperiments2023/5/15changetemperaturesupersaturation

goodsolubilitySolventselectionsolubilityvarieswiththetemperature

freezingpointofthesolvent目前二十四页\总数二十五页\编于十九点Slow/fastprecipitationfromsaturatedsolutionsmethod2023/5/15EvaporatethesolventsupersaturationSlow/fastrateofcrystallization

SolventselectionlowboilingpointsolventboilingpointDMF152.8ºCDMSO189ºCNMP202ºC目前二十五页\总数二十五页\编于十九点