目的 基于质量源于设计（quality by design，QbD）理念对红花颗粒进行制备工艺研究，并对颗粒进行质量控制。方法 以红花为模型，采用湿法制粒，以颗粒的羟基红花黄色素A保留率、总黄酮保留率、颗粒成型率、松密度、振实密度、相对均齐度指数、豪斯纳比、休止角、干燥失重及吸湿率作为评价指标，单因素结合Box-Behnken设计响应面法对颗粒制备工艺参数进行研究。采用物理指纹图谱法对红花颗粒各项物理属性指标进行综合表征，建立由7个指标（松密度、振实密度、相对均齐度指数、豪斯纳比、休止角、干燥失重及吸湿率）构成的颗粒物理指纹图谱，评价不同批次颗粒的质量一致性。结果 优选出红花颗粒制备工艺：药辅用量比为1：0.8，润湿剂（95%乙醇）用量为32%，于70℃干燥120 min。10批红花颗粒物理指纹图谱相似度均高于0.99。结论 建立的红花颗粒制备工艺稳定可行，物理质量标准科学合理，可以为中药制剂的研发提供新的思路。

Objective To study the prescription and preparation technology of Carthami Flos Granules and evaluate its physical quality based on quality by design. Methods Carthami Flos was used as a model drug. The evaluation indicators were retention rate of hydroxysafflor yellow A (HSYA) and total flavonoid, primary formation rate, bulk density, tap density, relative homogeneity index, Hausner ratio, angle of repose, loss on drying, and hygroscopicity. The single factor experiments and the Box-Behnken design response surface method were used to investigate the particle forming process parameters. The physical fingerprint of granules was constructed by seven indexes including bulk density, tap density, relative homogeneity index, Hausner ratio, angle of repose, loss on drying, and hygroscopicity. Results The optimum conditions were as follows:the dosage ratio of drug to adjuvant was 1︰0.8, the amount of wetting agent (95% ethanol) was 32%, and dried at 70℃ for 120 min. The similarity of the physical fingerprint of 10 batches of Carthami Flos Granules was higher than 0.99. Conclusion The prescription and preparation technology of Carthami Flos Granules and the physical quality were scientific and reasonable, which can provide ideas and methods for the research and development of Chinese materia medica.

北京市科技计划“十病十药”研发项目（Z151100003815019）