于佳琦;徐冰;黄雨妍;张志强;戴胜云;付静;乔延江;
YU Jia-qi;XU Bing;HUANG Yu-yan;ZHANG Zhi-qiang;DAI Sheng-yun;FU Jing;QIAO Yan-jiang;Department of Chinese Medicine Information Science, Beijing University of Chinese Medicine;Beijing Key Laboratory for Production Process Control and Quality Evaluation of Traditional Chinese Medicine, Beijing Municipal Science & Technology Commission;Beijing Tcmages Pharmaceutical Co., Ltd.;National and Regional Joint Engineering Research Center for Key Technologies of Chinese Medicine Formula Granules;National I

• 1:北京中医药大学中药信息学系
• 2:北京市科委中药生产过程控制与质量评价北京市重点实验室
• 3:北京康仁堂药业有限公司
• 4:中药配方颗粒关键技术国家地方联合工程研究中心

摘要(Abstract)：

该文采用在线浊度传感器技术,对中药颗粒剂溶化过程中溶液的浑浊程度进行量化表征。对探头测量位置和磁力搅拌的转速进行优化,结果搅拌转速选取400 r·min~(-1),探头位置在烧杯直径的1/4处时,测量结果准确可靠。收集105批市售中成药颗粒剂,按照《中国药典》要求进行溶化性检查,结果在5 min时间点,有57批颗粒完全溶化,对应浊度值在0～70 FTU;32批颗粒剂表现为轻微浑浊,对应浊度值在70～350 FTU;14批颗粒剂溶液浑浊,对应浊度值在350～2 000 FTU;2批颗粒剂溶液重度浑浊,对应浊度值>2 000 FTU。上述颗粒剂测试结果中,符合药典溶化性要求的批次数占比为84.76%,部分品种的溶化性仍有待改进。通过浊度传感器记录浊度值随时间变化的曲线(溶化行为曲线),按照溶化过程中崩解和溶解的重要程度,即崩解>溶解、崩解≈溶解、崩解<溶解,可将颗粒剂的溶化行为分为3类,通过颗粒剂溶化过程中机制的解析,为产品质量和工艺改进提供依据。
In this paper, the inline turbidity sensor technology was used to quantify the turbidity of the solution during the dissolution of Chinese medicine granules. The probe measurement position and the magnetic stirring speed were optimized. As a result, the stirring speed was 400 r·min~(-1), and the probe position was at 1/4 of the diameter of the beaker. The measurement results were accurate and reliable. Totally 105 batches of commercially available Chinese medicine granules were collected and dissolved according to the requirements of the Chinese Pharmacopoeia. At the time point of 5 min, 57 batches of granules were completely dissolved, and the corresponding turbidity values ranged between 0-70 FTU; 32 batches of granules showed a slight turbidity, and the corresponding turbidity values ranged between 70-350 FTU; 14 batches of granule solution were turbid, and the corresponding turbidity values ranged between 350-2 000 FTU; two batches of granule solution were heavily turbid, and the corresponding turbidity values were >2 000 FTU. Among the above results, the number of batches in line with the pharmacopoeia dissolution requirement was 84.76%, and the dissolution of some granules still needed to be improved. The turbidity sensor recorded the change curve of turbidity value over time(solubility behavior curve). The degree of important of disintegration and dissolution during the dissolution process showed disintegration > dissolution, disintegration≈dissolution, disintegration < dissolution. The dissolution behavior of the granules can be classified into three categories. The analysis of the mechanism in the process of granule solubility provides a basis for product process improvement.

关键词(KeyWords)： 颗粒剂;浊度传感器;溶化性;溶化机制;过程分析技术
granules;turbidity sensor;solubility;solubility mechanism;process analysis technique

Abstract:

Keywords:

基金项目(Foundation): 北京中医药大学科研项目(2019-JYB-JS-015);; 国家自然科学基金项目(81403112)

作者(Author): 于佳琦;徐冰;黄雨妍;张志强;戴胜云;付静;乔延江;
YU Jia-qi;XU Bing;HUANG Yu-yan;ZHANG Zhi-qiang;DAI Sheng-yun;FU Jing;QIAO Yan-jiang;Department of Chinese Medicine Information Science, Beijing University of Chinese Medicine;Beijing Key Laboratory for Production Process Control and Quality Evaluation of Traditional Chinese Medicine, Beijing Municipal Science & Technology Commission;Beijing Tcmages Pharmaceutical Co., Ltd.;National and Regional Joint Engineering Research Center for Key Technologies of Chinese Medicine Formula Granules;National I

Email:

DOI: 10.19540/j.cnki.cjcmm.20191219.304

参考文献(References)：

• [1] 袁哲,尹燕杰.浊度计用于中药可溶颗粒剂溶化性测定的探析 [J].中国药品标准,2015,16(4):285.
• [2] 李真,杨会芳,李德坤,等.红参提取液浊度测定方法及油脂类物质对浊度影响研究 [J].人参研究,2015,27(2):4.
• [3] 王彤,刘丽,李德坤,等.基于浊度测量技术的丹参药材质量快速评价方法 [J].现代中药研究与实践,2017,31(5):4.
• [4] CLOERN J E.Turbidity as a control on phytoplankton biomass and productivity in estuaries [J].Cont Shelf Res,1987,7(11/12):1367.
• [5] MORRISON J S,NOPHSKER M J,HASKELL R J.A combination turbidity and supernatant microplate assay to rank-order the supersaturation limits of early drug candidates [J].J Pharm Sci,2014,103(10):3022.
• [6] CLAIS S,BOULET G,VAN KERCKHOVEN M,et al.Comparison of viable plate count,turbidity measurement and real-time PCR for quantification of Porphyromonas gingivalis [J].Lett Appl Microbiol,2015,60(1):79.
• [7] CUI M,YANG C.Implementation of a digital optical phase conjugation system and its application to study the robustness of turbidity suppression by phase conjugation[J].Opt Express,2010,18(4):3444.
• [8] MARIF Y,BECHKI D,ZERROUKI M,et al.Estimation of atmospheric turbidity over Adrar city in Algeria [J].J King Saud Univ Sci,2019,31(2):143.
• [9] 万聪,邹燕娣,金瑚,等.浊度仪法快速测定菜籽油中蜡质含量 [J].中国油脂,2017,42(9):129.
• [10] 陈璇,侯玉嵩.30批中药可溶性颗粒剂的溶化性检查 [J].中国药房,2006 (14):1117.
• [11] 常艳,余方键,胡昌勤.2015年版《中国药典》澄清度检查法研究 [J].中国药学杂志,2017,52(9):802.
• [12] MUTCH G A,HAPGOOD K P,SHEN R,et al.An investigation on the dissolution qualities of foam granulated products [J].Powder Technol,2019 (343):693.
• [13] 徐冰,史新元,吴志生,等.论中药质量源于设计 [J].中国中药杂志,2017,42(5):1015.
• [14] 徐冰,史新元,罗赣,等.中药工业大数据关键技术与应用[J].中国中药杂志,2020,45(2):221.