基于质量源于设计理念的二冬汤颗粒制备工艺及质量控制

目的:基于质量源于设计(QbD)理念对二冬汤颗粒制备工艺进行研究,并对其质量进行控制。方法:设计L9(34)正交试验法,以出膏率、指标成分转移率、总多糖为评价指标,AHP-CRITIC混合加权法优选二冬汤最佳提取工艺；以成型性、溶化性、休止角、吸湿性为考察指标,采用星点设计-效应面法结合熵权法优化二冬汤颗粒成型工艺；以相对均齐指数、松密度、振实密度、水分、吸湿率、休止角、豪丝纳比为指标,建立物理指纹图谱,评价颗粒质量一致性；结果:二冬汤的最佳提取工艺为加水量12倍,不浸泡,提取3次,每次30 min。3批重复验证试验综合评分均数为54.24,RSD为1.09％；二冬汤颗粒的最佳成型工艺为,干膏粉与辅料比为1:0.6,润湿剂体积分数87％,润湿剂用量16％,在80°C下干燥30 min。5批颗粒物理指纹图谱相似度均大于0.99。结论:该法稳定可行,可为二冬汤工业化生产以及该制剂的进一步研究提供方向。

Preparation technology and quality control of Erdong Decoction granules based on quality by design concept

ABSTRACT: OBJECTIVE Based on the concept of quality by design (QbD), the preparation process of Erdong Decoction granules was studied and its quality was controlled. METHODS L9 (34) orthogonal test was designed, and the extraction process of Erdong Decoction was optimized by AHP-CRITIC mixed weighted method with the extract rate, index component transfer rate and total polysaccharide as evaluation indexes. Formability, melting ability, Angle of rest and hygroscopicity were used to optimize the forming process of Erdong Decoction granules by the combination of star design-effect surface method and entropy weight method. Using relative homogeneity index, bulk density, vibrational density, moisture, hygroscopicity, resting Angle and Hausenar ratio as indexes, physical fingerprint was established to evaluate the quality consistency of particles. RESULTS The optimal extraction process of Erdong decoction was to add 12 times of water without soaking and extract 3 times for 30 min each time. The average comprehensive score of the three batches of repeated verification tests was 54.24, and the RSD was 1.09%. The optimum molding process of Erdong Decoction granules was as follows: the ratio of dry paste powder to auxiliary material was 1:0.6, the volume fraction of wetting agent was 87%, the amount of wetting agent was 16%, and it was dried at 80°C for 30 min. The similarity of physical fingerprints of 5 batches of particles was greater than 0.99. CONCLUSION The method is stable and feasible, and can provide direction for the industrial production of Erdong decoction and the further study of the preparation.