药物晶型研究.ppt

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1、2021/7/27药物的多晶型研究2021/7/27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2021/7/27CrystalAsolidmaterialwhoseconstituentatoms,molecules,orionsarearrangedinanorderlyrepeatingpatternextendinginallthreespatialdimensions.Pharmaceuticalcrysta

2、lsMostdrugsaredevelopedascrystallineStabilityProcessabilityIPprotection什么是晶体？什么是多晶型？Polymorphismistheabilityofasolidmaterialtoexistinmorethanoneformorcrystalstructure.PolymorphsSoldphaseSamechemicalcompositionDifferentmoleculararrangementsInpractice,wearein

3、terestedinallthecrystallineandamorphousphasesforachemical/pharmaceutical2021/7/272021/7/272021/7/27多晶型研究对药物开发的重要性2021/7/27药物多晶型研究的重要性2021/7/272021/7/27如何筛选和选择药物的新晶型2021/7/272021/7/272021/7/27晶型的化学和物理分析手段2021/7/272021/7/272021/7/27Experiencesharingonpolymorp

4、hscreening——solventselection2021/7/27ThepurposeofpolymorphscreeningForInnovatorcompanies-selecttheoptimalsolid-stateofAPIfordevelopment-studyrelevantpolymorphsforIPprotectionForCROcompaniesbasedonthecustomersneeds-toidentifyasmanynewpolymorphs(includesolvat

5、e/hydrate)andamorphousformaspossible-ortofindthemoststableformThemethodofpolymorphscreening2021/7/27crystallizationcrystallizationfromsolution(slurry,anti-solventprecipitation,Solvent-thermalheating/coolingSlow/fastprecipitationfromsaturatedsolutions)recrys

6、tallizationfromaneatcompound(thermalheating/cooling,grinding,andhighpressure)polymorphscreening——crystallizationfromsolution2021/7/27degreeofsupersaturationandTemperatureareconsideredasthedrivingforceofcrystallisationdiversesolventsresultinthediscoveryofmo

7、repolymorphscrystallizationfromsolution——Solventselection2021/7/27SlurryAnti-solventprecipitationSolvent-thermalheating/coolingexperimentsSlow/fastprecipitationfromsaturatedsolutionsmethodSolventVisualsolubility(mg/mL)MeOHEtOHIPA1-ButanolACNMEKMIBKEtOAciPrO

8、AcMTBE2-MeTHFDMFNMPDMSOCH2Cl2Toluene1,4-DioxaneHeptaneTHFAcetoneWatercrystallizationfromsolution——rationalexperimentaldesign2021/7/27LimitedresourceHowtofindasmanynewpolymorphsandamorphousformaspossib