| 摘要: |
| 目的 总结胶囊剂溶出度试验方法设计的主要关注点，从处方囊壳、胶囊内含物以及包装的选择等方面讨论对胶囊剂溶出度的影响。方法 参考USP通则<1094>总结胶囊剂溶出度试验的设计考虑；汇总FDA溶出度数据库中胶囊剂溶出方法的收载情况；结合研究论文及实际工作提出溶出度方法开发的思考。结果 胶囊剂溶出度方法需重点关注溶出介质、溶出装置以及明胶交联问题；目前已上市胶囊剂溶出装置桨法比例高于篮法，有6.7%的胶囊剂使用酶法破除明胶交联。囊壳质量、胶囊内容物、包装等都可能影响胶囊剂溶出度，导致稳定性放置期间检测结果超限。结论 胶囊剂溶出度控制应坚持处方研发在前，检测检验在后的思路。开发期间重视可能影响胶囊剂溶出度的囊壳质量、胶囊内容物、包装等关键因素。在此基础上应合理设计胶囊剂溶出度试验方法，降低试验方法导致的溶出度结果差异。 |
| 关键词: 胶囊剂 USP<1094> 明胶交联 溶出度 风险评估 |
| DOI：10.13748/j.cnki.issn1007-7693.2021.04.023 |
| 分类号:R944.5 |
| 基金项目: |
|
| Discussion on Capsule Dissolution Method and Influencing Factors |
|
MA Junwei, AN Na
|
|
Center for Drug Evaluation, National Medical Products Administration, Beijing 100022, China
|
| Abstract: |
| OBJECTIVE To summarize the main concerns of the design of capsule dissolution testing methods, and discuss the influence on capsule dissolution from the aspects of capsule shell, capsule content, packaging materials, etc. METHODS Refer to USP General Chapter <1094> to summarize the design considerations of capsule dissolution testing. The capsule dissolution methods in FDA dissolution database were summarized; combining research papers and practical work, put forward the thinking of dissolution method development. RESULTS Capsule dissolution methods should focus on dissolution media, dissolution apparatus and gelatin cross-linking; the ratio of paddle apparatus in the marketed capsule was higher than that of basket apparatus, and 6.7% of capsule used enzymatic method to break gelatin cross-linking. The quality of the capsule shell, capsule content, packaging might affect the capsule dissolution, causing the failure of acceptance criteria during stability storage. CONCLUSION The capsule dissolution control is first determined by the formulation development and then by testing method. During the development, attention should pay to the key factors such as capsule shell quality, capsule content and packaging that may affect the capsule dissolution. On this basis, the capsule dissolution test method should be designed reasonably to reduce the difference of the dissolution results caused by the test method. |
| Key words: capsule USP <1094> gelatin cross-linking dissolution method risk assessment |
