胃肠道模拟器在药物溶出评价中的应用进展

Application progress of gastrointestinal simulator in dissolution evaluation

体外溶出试验在固体药物制剂的研发评价过程中发挥着重要的作用,生物药剂学分类系统(biopharmaceutics classification system,BCS)Ⅱ类弱碱性药物在胃肠道中可能存在过饱和和沉淀,影响制剂开发和药物吸收评估。胃肠道生理环境在很大程度上影响BCSⅡ类弱碱性药物的体内溶出速率,拥有动态特点的胃肠道模拟器(gastrointestinal simulator,GIS)由胃、十二指肠和空肠3个腔室组成,是一种实用的体外溶出装置,主要用于预测BCSⅡ类弱碱性药物的体内溶出、观测药物的过饱和和沉淀及监测减少沉淀措施的效果。在国外,GIS装置的应用和优化已经有了很多报道,但在国内关于GIS的应用研究较少。笔者对GIS的结构、介质、模型药物、分泌物等内容进行整理,并对其在溶出中的应用进行归纳总结,以期胃肠道模拟器在药物评价中可以得到更广泛的应用。

In vitro dissolution test plays an important role in the development and evaluation of solid pharmaceutical preparations.ClassⅡweakly alkaline drugs in biopharmaceutics classification system(BCS)may show supersaturation and precipitation in the gastrointestinal tract,which affect the development of preparations and the evaluation of drug absorption.The physiological environment of gastrointestinal tract greatly affects the dissolution rates of BCSⅡweakly alkaline drugs in vivo.The gastrointestinal simulator(GIS)with dynamic characteristics is composed of three chambers of stomach,duodenum and jejunum,which is a practical in vitro dissolution device,and mainly used to predict the dissolution of BCSⅡweakly alkaline drugs in vivo,observe the supersaturation and precipitation of drugs,and monitor the effect of precipitation reduction measures.There have been many reports on the application and optimization of GIS devices at abroad,but there are few studies on the application of GIS in China.The author sorted out the structure,media,model drugs,secretions and other contents of GIS,and summarized its application in dissolution,hoping that GIS can be more widely used in drug evaluation.