低溶解性药物平衡溶解度测定的影响因素研究  

Influencing Factors of Equilibrium Solubility Measurement of Low-solubility Drugs

作　　者：赵瑜 姚尚辰[1,2] 金少鸿 尹利辉[1,2] 许明哲 ZHAO Yu;YAO Shang-chen;JIN Shao-hong;YIN Li-hui;XU Ming-zhe(Institutes for Chemical Drug Control,National Institutes for Food and Drug Control,Beijing 102629,China;NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs,National Institutes for Food and Drug Control,Beijing 102629,China)

机构地区：[1]中国食品药品检定研究院化学药品检定所,北京102629 [2]中国食品药品检定研究院化学药品质量研究与评价重点实验室,北京102629

出　　处：《中国药学杂志》2020年第20期1717-1721,共5页Chinese Pharmaceutical Journal

摘　　要：目的探讨经典摇瓶法测定药物平衡溶解度实验中的影响因素,为WHO平衡溶解度实验程序指南的关键技术提出补充性建议。方法以头孢克肟和利福平为例,饱和摇瓶法条件:水浴37℃120 r·min^-1条件下,加入过量10%的固体,使达饱和,以高效液相色谱法测定饱和浓度,计算溶解度体积,进行溶解性判别。结果头孢克肟和利福平均为低溶解性药物。结论药物的稳定性,溶解体积,投样量、药物溶解速度和平衡时间之间的关系等对低溶解性药物平衡溶解度测定均有影响,本实验对"WHO指南"相关关键技术提出建议。OBJECTIVE To explore the influencing factors of the classic shake-flask method in the determination of drug equilibrium solubility,and provide supplementary suggestions for the key techniques of WHO guidelines of equilibrium solubility experiment procedure.METHODS Cefixime and rifampicin were taken as examples,and the conditions of saturated shake-flask method was as follows:in water bath at 37℃at shaking speed of 120 r·min^-1,10%excess solids were added to the saturated system.High performance liquid chromatography was used for determination of saturation concentration.Then the dissolubility volumes were calculated and the solubility classification was performed.RESULTS Cefixime and rifampicin were both judged to be low-solubility drugs.CONCLUSION The stability of the drug,the volume of dissolution,the amount of excess solid,and the relationship between the rate of drug dissolution and the equilibrium time all have impacts on the determination of the equilibrium solubility of low-solubility drugs,and some recommendations on key technologies are made for the WHO guideline.

关 键 词：平衡溶解度 饱和摇瓶法 低溶解性药物 头孢克肟 利福平 

分 类 号：R917[医药卫生—药物分析学]