优选药物晶型研究演示ppt
合集下载
相关主题
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
2020/10/19
crystallization
crystallization from solution
(slurry, anti-solvent precipitation , Solvent-thermal heating/cooling Slow/fast precipitation from saturated solutions)
2020/10/19
Experience sharing on polymorph screening ——solvent selection
2020/10/19
For Innovator companies - select the optimal solid-state of API for development -study relevant polymorphs for IP protection
PharmaceuticHale Waihona Puke Baidul crystals
Most drugs are developed as crystalline • Stability • Processability • IP protection
2020/10/19
什么是多晶型？
• Polymorphism is the ability of a solid material to exist in more than one form or crystal structure.
• degree of supersaturation and Temperature are considered as the driving force of crystallisation
• diverse solvents result in the discovery of more polymorphs
2020/10/19
crystallization from solution——
Solvent selection
Solvent MeOH
EtOH
• Slurry
IPA 1-Butanol
ACN
• Anti-solvent precipitation
MEK
MIBK
EtOAc
• Solvent-thermal
2020/10/19
2020/10/19
多晶型研究对药物开发的重要性
2020/10/19
药物多晶型研究的重要性
2020/10/19
2020/10/19
2020/10/19
如何筛选和选择药物的新晶型
2020/10/19
2020/10/19
晶型的化学和物理分析手段
2020/10/19
2020/10/19
2020/10/19
Slurry
——solvent selection
• Make sure the sample is suspension
• solvent/mixed solvents solubility is poor
（优选）药物晶型研究
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
2020/10/19
什么是晶体？
Crystal
A solid material whose constituent atoms,molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions.
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
For 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 form
Water
2020/10/19
Visual solubility (mg/mL)
crystallization from solution——
rational experimental design
• Limited resource
•
？ How to find as many new polymorphs and
iPrOAc
heating/cooling experiments
MTBE
2-MeTHF
• Slow/fast precipitation from
DMF
saturated solutions method
NMP
DMSO
CH2Cl2 Toluene
1,4-Dioxane
Heptane
THF
Acetone
• Polymorphs
▪ Sold phase ▪Same chemical composition ▪Different molecular arrangements
• In practice, we are interested in all the crystalline and amorphous phases for a chemical/pharmaceutical
recrystallization from a neat compound
(thermal heating/cooling, grinding , and high pressure )
2020/10/19
polymorph screening —— crystallization from solution
crystallization
crystallization from solution
(slurry, anti-solvent precipitation , Solvent-thermal heating/cooling Slow/fast precipitation from saturated solutions)
2020/10/19
Experience sharing on polymorph screening ——solvent selection
2020/10/19
For Innovator companies - select the optimal solid-state of API for development -study relevant polymorphs for IP protection
PharmaceuticHale Waihona Puke Baidul crystals
Most drugs are developed as crystalline • Stability • Processability • IP protection
2020/10/19
什么是多晶型？
• Polymorphism is the ability of a solid material to exist in more than one form or crystal structure.
• degree of supersaturation and Temperature are considered as the driving force of crystallisation
• diverse solvents result in the discovery of more polymorphs
2020/10/19
crystallization from solution——
Solvent selection
Solvent MeOH
EtOH
• Slurry
IPA 1-Butanol
ACN
• Anti-solvent precipitation
MEK
MIBK
EtOAc
• Solvent-thermal
2020/10/19
2020/10/19
多晶型研究对药物开发的重要性
2020/10/19
药物多晶型研究的重要性
2020/10/19
2020/10/19
2020/10/19
如何筛选和选择药物的新晶型
2020/10/19
2020/10/19
晶型的化学和物理分析手段
2020/10/19
2020/10/19
2020/10/19
Slurry
——solvent selection
• Make sure the sample is suspension
• solvent/mixed solvents solubility is poor
（优选）药物晶型研究
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
2020/10/19
什么是晶体？
Crystal
A solid material whose constituent atoms,molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions.
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
For 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 form
Water
2020/10/19
Visual solubility (mg/mL)
crystallization from solution——
rational experimental design
• Limited resource
•
？ How to find as many new polymorphs and
iPrOAc
heating/cooling experiments
MTBE
2-MeTHF
• Slow/fast precipitation from
DMF
saturated solutions method
NMP
DMSO
CH2Cl2 Toluene
1,4-Dioxane
Heptane
THF
Acetone
• Polymorphs
▪ Sold phase ▪Same chemical composition ▪Different molecular arrangements
• In practice, we are interested in all the crystalline and amorphous phases for a chemical/pharmaceutical
recrystallization from a neat compound
(thermal heating/cooling, grinding , and high pressure )
2020/10/19
polymorph screening —— crystallization from solution