闵红 高翔 周志云 贺聪莹 安凤秋

[摘要]目的调查目前市面上软膏剂的水分活度（ aw ）分布状况，为“水分活度测定在非无菌制剂中的应用指导原则”提供数据支撑。方法2019年8月在西安市各大药店采集43家生产企業34个品种共102批次软膏剂，并在25℃下对其 aw 进行检测。结果软膏剂的平均 aw 分布在0.0326～0.9804。去除离群值后，软膏剂平均 aw 的95%置信区间为0.7013～0.7661。结论对高 aw 软膏剂研发提出优化处方原则，提高自我防腐能力;对低 aw 软膏剂提出减少释放检验频次原则，合理微生物控制策略;软膏剂 aw 分布规律为《中国药典》“水分活度测定在非无菌制剂中的应用指导原则”提供坚实的数据支撑。

[关键词]软膏剂;水分活度（ aw ）;微生物安全评价;应用指导原则

[中图分类号] R283.6  [文献标识码] A   [文章编号]2095-0616（2021）23-0074-04

Distribution law of water activity of ointment and application guidance in pharmaceutical industry

MIN  Hong1，2      GAO  Xiang1      ZHOU  Zhiyun1，2      HE  Congying1，2      AN  Fengqiu3

1.Shaanxi Institute for Food and Drug Control， Shaanxi， Xi'an 710065， China;2.Key Laboratory of Pharmaceutical Microbiological Detection Technology， National Medical Products Administration， Shaanxi， Xi'an 710065， China;3.School of Environmental and Chemical Engineering， Xi'an Polytechnic University， Shaanxi， Xi'an 710048， China

[Abstract] Objective To investigate the distribution of water activity （aw） of ointments in the market at present， and to provide data support for "Guiding Principles of Water Activity Determination in Non-sterile Preparations". Methods In August 2019， 102 batches of ointments of 34 varieties from 43 manufacturing enterprises were collected from major pharmacies in Xi'an， and their aw  was tested at 25℃. Results The average aw  distribution of ointment ranged from 0.0326 to 0.9804. After removing outliers， the 95% confidence interval of average aw  of ointment was from 0.7013 to 0.7661. Conclusion The principle of optimizing prescription is put forward for the research and development of high aw  ointment to improve self-preservation ability. For low aw ointment， the principle of reducing release test frequency and rational microbial control strategy were put forward. The distribution law of ointment aw  provides solid data support for "Guiding Principles of Water Activity Determination in Non-sterile Preparations" in Chinese Pharmacopoeia.

[Key words] Ointment; Water activity （aw）; Microbial safety evaluation; Application guidance principles

水分活度（ aw ）是相同温度下样品中水分的饱和蒸汽压和纯水饱和蒸汽压的比值[1-2]。aw 已经在食品和化妆品行业微生物安全评价方面取得了广泛研究与应用[3-5]，但对于制药行业是一个相对崭新的概念。目前，美国药典<1112>章节已收载“非无菌制剂水分活度测定的应用研究”，其内容涵盖了水分活度的概念、水分活度与微生物的关系、代表性微生物生长所需最低 aw、水分活度在制药行业的应用、对代表性剂型药物推荐了微生物控制策略等方面内容[1]，而《中国药典》2020年版在 aw 相关内容仍属空白。

本研究调查43家生产企业34个品种共102批次的上市软膏剂的 aw 分布规律。根据软膏剂 aw 分布规律，首先评估软膏剂的潜在污染菌和……