口服固体制剂溶出方法建立和验证的技术探讨

Discussion of development and validation of dissolution methods for solid oral dosage forms

体外溶出检查通常被认为可反映药物的体内溶出行为和生物利用度情况,其在药物制剂研发和上市产品的质量控制中发挥着巨大的作用。一种溶出度实验方法的建立,需要综合考虑药物的物理化学性质和制剂学特征,确立合适的溶出条件以模拟药物的体内溶出行为。新建立的溶出方法不仅需要具有良好的准确性和耐用性,还要能区分不同质量属性的药物制剂。本文依据国内外药品监管机构关于建立和验证药物溶出方法的最新指导原则,通过查阅文献,综述了口服固体制剂溶出方法建立和溶出度标准制定的常见问题及研究进展,以期为药物溶出方法的建立和验证提供参考。

It is generally assumed that study of in vitro dissolution can reveal the in vivo behavior and bioavailability of a drug. The dissolution test indisputably plays a vital role in the research and development of pharmaceutical preparations as well as routine quality control of approved drugs. In order to develop an ideal dissolution method, the physicochemical properties of drug and the characteristics of its dosage form should be considered, and a proper dissolution condition be established to simulate the in vivo dissolution behavior of drugs. The new dissolution method should have the required characteristics of accuracy and durability, but also could distinguish pharmaceutic preparations with different quality. In recent years, there have been more and more reports on the establishment and verification of dissolution methods for oral solid dosage forms. However, there is very few review articles on the topic. According to the latest guidelines by domestic and foreign drug organizations, this review paper is prepared to summarize the most important skills and progress in the development of dissolution methods for oral solid preparations. The aim is to provide a reference for the development and validation of new dissolution methods.