藥物晶型研究演示

（優(yōu)選）藥物晶型研究目前一頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15提綱什么是晶體，多晶型？多晶型研究對藥物開發(fā)的重要性如何篩選和選擇藥物的新晶型多晶型的主要分析手段晶型篩選實(shí)驗(yàn)的經(jīng)驗(yàn)分享----溶劑選擇目前二頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15Crystal

Asolidmaterialwhoseconstituentatoms,molecules,orionsarearrangedinanorderlyrepeatingpatternextendinginallthreespatialdimensions.PharmaceuticalcrystalsMostdrugsaredevelopedascrystallineStabilityProcessabilityIPprotection什么是晶體？目前三頁\總數(shù)二十五頁\編于十九點(diǎn)什么是多晶型？

Polymorphismistheabilityofasolidmaterialtoexistinmorethanoneformorcrystalstructure.PolymorphsSoldphaseSamechemicalcompositionDifferentmoleculararrangementsInpractice,weareinterestedinallthecrystallineandamorphousphasesforachemical/pharmaceutical2023/5/15目前四頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15目前五頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15多晶型研究對藥物開發(fā)的重要性目前六頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15藥物多晶型研究的重要性目前七頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15目前八頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15目前九頁\總數(shù)二十五頁\編于十九點(diǎn)如何篩選和選擇藥物的新晶型目前十頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15目前十一頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15目前十二頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15晶型的化學(xué)和物理分析手段目前十三頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15目前十四頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15目前十五頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15Experiencesharingonpolymorphscreening——solventselection目前十六頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15ThepurposeofpolymorphscreeningForInnovatorcompanies-selecttheoptimalsolid-stateofAPIfordevelopment-studyrelevantpolymorphsforIPprotectionForCROcompaniesbasedonthecustomersneeds-toidentifyasmanynewpolymorphs(includesolvate/hydrate)andamorphousformaspossible-ortofindthemoststableform

目前十七頁\總數(shù)二十五頁\編于十九點(diǎn)Themethodofpolymorphscreening2023/5/15crystallizationcrystallizationfromsolution(slurry,anti-solventprecipitation,Solvent-thermalheating/coolingSlow/fastprecipitationfromsaturatedsolutions)recrystallizationfromaneatcompound(thermalheating/cooling,grinding,andhighpressure)目前十八頁\總數(shù)二十五頁\編于十九點(diǎn)polymorphscreening——

crystallizationfromsolution2023/5/15degreeofsupersaturationandTemperatureareconsideredasthedrivingforceofcrystallisationdiversesolventsresultinthediscoveryofmorepolymorphs目前十九頁\總數(shù)二十五頁\編于十九點(diǎn)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

目前二十頁\總數(shù)二十五頁\編于十九點(diǎn)crystallizationfromsolution——

rationalexperimentaldesign2023/5/15Limitedresource

Howtofindasmanynewpolymorphsand

amorphousformaspossibleAPIpropertiesdifferentsolubilityinthesolvent

poorsolubilityorgoodsolubilitySolventproperties

Polarity-differentsortofsolvents(alcohols,ethers,esteretc.)BoilingpointFreezingpointToxicitymiscibility？目前二十一頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15Slurry——solventselectionMakesurethesampleissuspension

solvent/mixedsolventssolubilityispoor目前二十二頁\總數(shù)二十五頁\編于十九點(diǎn)2023/5/15Anti-solventprecipitation

—solventselectionPreparesolventgoodsolubilityAnti-solventselectionPoorsolubilitypolaritymiscibility

miscibilityWaterDMFHeptaneACN1,4-DioxaneMTBEDMSO目前二十三頁\總數(shù)二十五頁\編于十九點(diǎn)Solvent-thermal

heating/coolingexperiments2023/5/15changetemperaturesupersaturation

goodsolubilitySolventselectionsolubilityvarieswiththetemperature

freezingpointofthesolvent目前二十四頁\總數(shù)二十五頁\編于十九點(diǎn)Slow/fastprecipitationfromsaturatedsolutionsmethod2023/5/15Evaporatethesolvent