基于水分活度的非无菌中药制剂微生物控制策略研究

Study on Microbiological Control Strategy of Non-sterile Traditional Chinese Medicine Preparation Based on Water Activity

关键词:  中药制剂  水分活度  微生物污染  微生物控制  质量控制

Key words:  Traditional Chinese medicine preparations  water activity  microbial contamination  microbial control  quality control

摘要:

目的 建立基于水分活度(a_w)的非无菌中药制剂微生物控制策略。方法 测定11种中药剂型的水分活度分布，采用水分活度为0.328，0.529，0.753，0.902，0.973的条件下放置的方法分析胶囊剂、丸剂等中药制剂水分活度和需氧菌总数、霉菌及酵母菌总数的变化规律，建立中药制剂的微生物控制策略。结果 在GMP条件下生产的中药制剂，可根据a_w将非无菌中药制剂分为4类，评估微生物生长繁殖风险，采取科学的微生物控制策略。一类产品a_w≥0.90，进行TAMC，TYMC以及该剂型规定的控制菌和其他具有潜在危害的微生物测试；二类产品0.90 > a_w≥0.85，进行TAMC，TYMC和金黄色葡萄球菌测试；三类产品0.85 > a_w≥0.60，进行TAMC、TYMC测试；四类产品a_w < 0.60，可结合风险评估，逐步研究减少测试的控制方案。结论 基于水分活度的中药制剂分类控制策略为微生物控制提供了新思路，在降低中药制剂生物负载的前提下，可通过控制水分活度降低中药制剂生产、运输、储存等过程的微生物生长繁殖风险，进而提高非无菌中药制剂的微生控制水平。

Abstract:

OBJECTIVE To establish a microbiological control strategy for non-sterile Chinese medicine preparations based on water activity(a_w).METHODS The water activity and the total number of aerobic bacteria of 11 kinds of traditional Chinese medicines(TCM) were measured by the method of placing samples under series of water activity conditions 0.328, 0.529, 0.753, 0.902, 0.973, the water activity distribution and the change rule of the total number of molds and yeasts of 11 kinds of Traditional Chinese Medicines was figure out.RESULTS TCM preparations produced in GMP conditions could be classified into 4 categories according to a_w, assessing the risk of microbial growth and reproduction, and adopting scientific microbial control strategies. For the first type of product a_w≥0.90, test TAMC, TYMC and the prescribed control bacteria and other potentially harmful microbial tests, for the second type of product 0.90 > a_w≥0.85, test TAMC, TYMC and Staphylococcus aureus test, for the third type of product 0.85 > a_w≥0.60, test TAMC and TYMC, for the fourth type of products a_w < 0.60, could be combined with risk assessment, and gradually study the control plan to reduce the test.CONCLUSION The classification of TCM preparations based on a_w provides new ideas for microbial control. Under the premise of reducing the bioburden of TCM preparations, the risk of microbial growth and reproduction during the production, transportation, and storage of TCM preparations can be reduced by controlling the a_w, thereby increasing the level of microbiological control of non-sterile TCM preparations.