强制降解试验在药物研发中的应用

Application of Forced Degradation Testing in Drug Development

关键词:  强制降解  药物研发  降解条件  注册申报

Key words:  forced degradation  drug development  degradation conditions  registration

摘要:

目的 阐述强制降解试验研究现状，汇总各强制降解试验基本条件，为药物研发提供借鉴和参考。方法 汇总实际工作和文献中药物降解基本方法，分析药品注册申报各阶段对降解研究的要求。结果 现阶段各国监管机构没有提出统一明确的强制降解试验条件，药物的降解条件与药物分子结构及制剂处方相关。结论 强制降解研究可以帮助确定药物的降解途径并解析降解产物，为药物安全性和毒理学研究提供支持，也为稳定性指示分析方法、药物处方、包装选择和储存条件的开发提供支持。从药物研发早期到后期，强制降解需要不断完善。

Abstract:

OBJECTIVE To expound the present situation of forced degradation, summarize the basic conditions of forced degradation testing, and provide guidance for drug research and development. METHODS The basic methods of drug forced degradation in actual work and literature were summarized, and the requirements of forced degradation at different phase of drug registration were analyzed. RESULTS At this stage, national regulatory agencies did not propose uniform conditions for forced degradation testing. The degradation conditions of the drug were related to the molecular structure and the formulation of the drug. CONCLUSION Forced degradation studies can help identify drug degradation pathways and analyze degradants, support drug safety and toxicology study, and support the development of stability indicator analytical methods, drug formulation, packaging and storage conditions. From the early to the late stage of drug development, forced degradation needs to be continuously improved.