基于QbD理念的双叶枇杷颗粒成型工艺优化及物理指纹图谱研究

Optimization of molding process and physical fingerprint of Shuangye pipa granules based on QbD concept

目的 基于质量源于设计(QbD)理念优化双叶枇杷颗粒的成型工艺,并进行物理指纹图谱分析。方法 以双叶枇杷颗粒干浸膏粉为主药,颗粒的总黄酮保留率、吸湿率、溶化率、休止角和成型率为评价指标,基于单因素实验结合熵权法和BoxBehnken响应面设计优化双叶枇杷颗粒的成型工艺,并进行验证。通过8个二级物理指标(相对均齐度、水分、吸湿率、豪斯纳比、休止角、松密度、振实密度和孔隙率)对最优成型工艺制得的10批双叶枇杷颗粒进行物理指纹图谱分析。结果 在固定辅料为可溶性淀粉-麦芽糊精-甘露醇(质量比为1∶1∶1),润湿剂(乙醇)质量分数为95%的条件下,双叶枇杷颗粒的最优成型工艺为药辅比1∶0.8(m/m),95%乙醇用量37%,干燥温度59℃,干燥时间28 min。3次验证实验结果显示,平均综合得分为0.879 6分,与模型预测值(0.881 9分)的RSD为1.97%。10批双叶枇杷颗粒的物理指纹图谱与对照物理指纹图谱的相似度均大于0.99。结论 本研究所优化的成型工艺稳定可行,以此工艺制得的双叶枇杷颗粒物理性状稳定、可控。

OBJECTIVE To optimize the molding process of Shuangye pipa granules based on the concept of quality by design(QbD) and analyze its physical fingerprint.METHODS The dry extract of Shuangye pipa granules was used as the main drug.The retention rate of total flavonoid,moisture absorption rate,dissolution rate,angle of repose and molding rate of the granules were selected as evaluation indexes.The single-factor test combined with the entropy weight method and Box-Behnken response surface design was used to optimize the molding process,and validation test was conducted.The physical fingerprints of 10 batches of Shuangye pipa granules prepared by the optimal process were comprehensively analyzed by eight secondary physical indexes(relative homogeneity,moisture,moisture absorption rate,Hausner ratio,angle of repose,bulk density,tap density and porosity).RESULTS The optimal molding process of Shuangye pipa granules was as follows:soluble starch-maltodextrin-mannitol was 1∶1∶1(m/m/m),95% ethanol was as wetting agent and the amount of it was 37%,the drug-assisted ratio was 1∶0.8(m/m),the drying temperature was 59 ℃,drying time was 28 min.The results of 3 validation tests showed that the average comprehensive score was 0.879 6,the RSD of which with prediction value(0.881 9 score) was 1.97%.The similarity between the physical fingerprints of 10batches of Shuangye pipa granules and the control physical fingerprint was higher than 0.99.CONCLUSIONS The optimized molding process of Shuangye pipa granules is stable and feasible,and the physical property of Shuangye pipa granules is stable and controllable.