药物晶型研究PPT课件.ppt

2020 4 8 药物的多晶型研究 1 2020 4 8 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 2 2020 4 8 CrystalAsolidmaterialwhoseconstituentatoms molecules orionsarearrangedinanorderlyrepeatingpatternextendinginallthreespatialdimensions PharmaceuticalcrystalsMostdrugsaredevelopedascrystallineStabilityProcessabilityIPprotection 什么是晶体 3 什么是多晶型 Polymorphismistheabilityofasolidmaterialtoexistinmorethanoneformorcrystalstructure PolymorphsSoldphaseSamechemicalcompositionDifferentmoleculararrangementsInpractice weareinterestedinallthecrystallineandamorphousphasesforachemical pharmaceutical 2020 4 8 4 2020 4 8 5 2020 4 8 多晶型研究对药物开发的重要性 6 2020 4 8 药物多晶型研究的重要性 7 2020 4 8 8 2020 4 8 9 如何筛选和选择药物的新晶型 2020 4 8 10 2020 4 8 11 2020 4 8 12 2020 4 8 晶型的化学和物理分析手段 13 2020 4 8 14 2020 4 8 15 2020 4 8 Experiencesharingonpolymorphscreening solventselection 16 2020 4 8 Thepurposeofpolymorphscreening ForInnovatorcompanies selecttheoptimalsolid stateofAPIfordevelopment studyrelevantpolymorphsforIPprotectionForCROcompaniesbasedonthecustomersneeds toidentifyasmanynewpolymorphs includesolvate hydrate andamorphousformaspossible ortofindthemoststableform 17 Themethodofpolymorphscreening 2020 4 8 crystallization crystallizationfromsolution slurry anti solventprecipitation Solvent thermalheating coolingSlow fastprecipitationfromsaturatedsolutions recrystallizationfromaneatcompound thermalheating cooling grinding andhighpressure 18 polymorphscreening crystallizationfromsolution 2020 4 8 degreeofsupersaturationandTemperatureareconsideredasthedrivingforceofcrystallisationdiversesolventsresultinthediscoveryofmorepolymorphs 19 crystallizationfromsolution Solventselection 2020 4 8 SlurryAnti solventprecipitationSolvent thermalheating coolingexperimentsSlow fastprecipitationfromsaturatedsolutionsmethod 20 crystallizationfromsolution rationalexperimentaldesign 2020 4 8 LimitedresourceHowtofindasmanynewpolymorphsandamorphousformaspossibleAPIpropertiesdifferentsolubilityinthesolventpoorsolubilityorgoodsolubilitySolventpropertiesPolarity differentsortofsolvents alcohols ethers esteretc BoilingpointFreezingpointToxicitymiscibility 21 2020 4 8 Slurry solventselection Makesurethesampleissuspensionsolvent mixedsolventssolubilityispoor 22 2020 4 8 Anti solventprecipitation solventselection Preparesolventgoodsolubility Anti solventselection Poorsolubility polarity miscibility miscibilityWaterDMFHeptaneACN1 4 DioxaneMTBEDMSO 23 Solvent thermalheating coolingexperiments 2020 4 8 changetemperaturesupersaturationgoodsolubilitySolventselectionsolubilityvarieswiththetemperaturefreezingpointofthesolvent 24 Slow fastprecipitationfromsaturatedsolutionsmethod 2020 4 8 EvaporatethesolventsupersaturationSlow fastrateofcrystallizationSolventselectionlowboilingpoint 25 Summary Solventselection 2020 4 8 keypointofthemethods