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资料仅供参考,不当之处，请联系改正。提纲提纲F什么是晶体，多晶型？F多晶型研究对药物开发的重要性F如何筛选和选择药物的新晶型F多晶型的主要分析手段F晶型筛选实验的经验分享-溶剂选择2024/7/6提纲什么是晶体，多晶型？2023/8/121资料仅供参考,不当之处，请联系改正。Crystal A solid material whose constituent atoms,molecules,or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions.Pharmaceutical crystals Most drugs are developed as crystallineStabilityProcessabilityIP protection 什么是晶体？什么是晶体？2024/7/6Crystal什么是晶体？2023/8/122资料仅供参考,不当之处，请联系改正。什么是多晶型？什么是多晶型？Polymorphism is the ability of a solid material to exist in more than one form or crystal structure.Polymorphs Sold phaseSame chemical compositionDifferent molecular arrangements In practice,we are interested in all the crystalline and amorphous phases for a chemical/pharmaceutical2024/7/6什么是多晶型？Polymorphism is the ab3资料仅供参考,不当之处，请联系改正。2024/7/62023/8/124资料仅供参考,不当之处，请联系改正。多晶型研究对药物开发的重要性2024/7/62023/8/125资料仅供参考,不当之处，请联系改正。药物多晶型研究的重要性药物多晶型研究的重要性2024/7/6药物多晶型研究的重要性2023/8/126资料仅供参考,不当之处，请联系改正。2024/7/62023/8/127资料仅供参考,不当之处，请联系改正。2024/7/62023/8/128资料仅供参考,不当之处，请联系改正。如何筛选和选择药物的新晶型如何筛选和选择药物的新晶型9资料仅供参考,不当之处，请联系改正。2024/7/62023/8/1210资料仅供参考,不当之处，请联系改正。2024/7/62023/8/1211资料仅供参考,不当之处，请联系改正。晶型的化学和物理分析手段晶型的化学和物理分析手段2024/7/6晶型的化学和物理分析手段2023/8/1212资料仅供参考,不当之处，请联系改正。2024/7/62023/8/1213资料仅供参考,不当之处，请联系改正。2024/7/62023/8/1214资料仅供参考,不当之处，请联系改正。Experience sharing on polymorph screening solvent selection2024/7/6Experience sharing on polymorp15资料仅供参考,不当之处，请联系改正。The purpose of polymorph screeningFor Innovator companies -select the optimal solid-state of API for development -study relevant polymorphs for IP protectionFor CRO companies based on the customers needs -to identify as many new polymorphs(include solvate/hydrate)and amorphous form as possible -or to find the most stable form2024/7/6The purpose of polymorph scree16资料仅供参考,不当之处，请联系改正。The method of polymorph screeningcrystallizationcrystallization from solution(slurry,anti-solvent precipitation,Solvent-thermal heating/coolingSlow/fast precipitation from saturated solutions)recrystallization from a neat compound(thermal heating/cooling,grinding,and high pressure)2024/7/6The method of polymorph screen17资料仅供参考,不当之处，请联系改正。polymorph screening crystallization from solutiondegree of supersaturation and Temperature are considered as the driving force of crystallisation diverse solvents result in the discovery of more polymorphs2024/7/6polymorph screening 18资料仅供参考,不当之处，请联系改正。crystallization from solution Solvent selectionSlurryAnti-solvent precipitation Solvent-thermal heating/cooling experiments Slow/fast precipitation from saturated solutions method SolventVisual solubility(mg/mL)MeOHEtOHIPA1-ButanolACNMEKMIBKEtOAciPrOAcMTBE2-MeTHFDMFNMPDMSOCH2Cl2Toluene1,4-DioxaneHeptaneTHFAcetoneWater2024/7/6crystallization from solution19资料仅供参考,不当之处，请联系改正。crystallization from solution rational experimental designLimited resource How to find as many new polymorphs and amorphous form as possible API properties different solubility in the solvent poor solubility or good solubility Solvent properties Polarity-different sort of solvents(alcohols,ethers,ester etc.)Boiling point Freezing point Toxicity miscibility？2024/7/6crystallization from solution20资料仅供参考,不当之处，请联系改正。Slurry solvent selectionMake sure the sample is suspension solvent/mixed solvents solubility is poor2024/7/6Slurry solv21资料仅供参考,不当之处，请联系改正。Anti-solvent precipitation solvent selection Prepare solvent good solubilityAnti-solvent selectionPoor solubilitypolaritymiscibility miscibility Water DMF Heptane ACN 1,4-Dioxane MTBE DMSO2024/7/6Anti-solvent precipitation 22资料仅供参考,不当之处，请联系改正。Solvent-thermal heating/cooling experimentschange temperature supersaturation good solubility Solvent selection solubility varies with the temperature freezing point of the solvent 2024/7/6Solvent-thermal heating/cool23资料仅供参考,不当之处，请联系改正。Slow/fast precipitation from saturated solutions methodEvaporate the solvent supersaturationSlow/fast rate of crystallization Solvent selection low boiling point solventboiling pointDMF 152.8 CDMSO189 CNMP202 C2024/7/6Slow/fast precipitation from s24资料仅供参考,不当之处，请联系改正。SummarySolvent selectionkey point of the method select appropriate solvent different solubility in the solventsolvent propertiesmiscibilitybetween solvents Polarityboiling pointfreezing pointToxicity2024/7/6SummarySolvent selectionkey p25
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