基于QbD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(quality by design,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；以成型率、溶化率、休止角、吸湿率为考察指标，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：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℃下干燥30 min。5批颗粒物理指纹图谱相似度均>0.99。结论 该法稳定可行，可为二冬汤颗粒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 QbD

OBJECTIVE To study the preparation technology based on quality by design (QbD) concept of Erdong decoction particles, and to control its quality. METHODS Design L9(3⁴) orthogonal test method, 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. Taking ratio of briquetting, dissolution rate, angle of repose and moisture absorption rate as indexes, the central composite design-response surface methodology method combined with entropy weight method was used to optimize the forming process of Erdong decoction granules. The relative homogeneity index, bulk density, vibration density, moisture, hygroscopicity, angle of reposition and Hausner ratio were used as indicators to establish a physical fingerprint to evaluate particle quality consistency. RESULTS The optimal extraction process of Erdong decoction was to add 12 times of water without soaking and extract it 3 times for 30 min each time. The mean comprehensive score of the three batches of repeated validation 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 ℃ for 30 min. The similarity of physical fingerprints of 5 batches of particles was>0.99. CONCLUSION The method is stable and feasible, which can provide direction for the industrial production of Erdong decoction granules and the further research of this preparation.