创新药研发流程课件.ppt

制剂-处方前研究(preformulation) Property Description pKa 电离常数 Measure of acidity of a functional group in the API chemical structure; applicable for compounds with ionizable functional groups. Importantfor stability and possible salt formation studies. Solubility 溶解度 Amount dissolved in water or other relevant media. Temperatures usedinclude room temperature (around 22 °C) and body temperature(around 37 °C). pH solubility profile 不同pH溶液中的溶解度 Amount dissolved at different acidic (low pH) and basic (high pH)conditions. Physiological pH ranges from 1.2 to 7.4, but other valuesmay also be tested. Temperatures used include room temperature(around 22 °C) and body temperature (around 37 °C). Intrinsic dissolution rate 固有溶出度 Rate at which the material dissolves in a relevant media, such as water, simulated gastric fluid (SGF), or simulated intestinal (SIF). Temperatures used include room temperature (around 22 °C) and body temperature (around 37 °C) Partition coefficient (log P) 油水分配系数 Measure of how well a substance partitions between lipids and water, which can help predict how well a compound will pass through cell membranes. Permeability 渗透性 Evaluate the drug’s potential for transport (permeation) through the intestinal wall . 制剂-处方前研究(preformulation) Property Description Crystallinity 结晶度 Determine if material is crystalline or amorphous. Crystal form 晶型 Determine the structure of a crystalline material Melting point 熔点 Determine the temperature where the drug substance melts. Solvent content 水分/溶剂含量 Amount of water or solvents contained in the drug substance Water uptake(hygroscopicity) 引湿性 Amount of water sorbed at over a wide range of relative humidities todetermine any special handling properties that may be needed. Stability studies 稳定性研究 Determine chemical and physical stability at elevated temperature and humidity conditions. Excipients compatibility study 原辅料相容性 investigate any interactions between the drug substance and excipients that may lead to changes, s