目的 基于质量源于设计（quality by design，QbD）理念，以山楂配方颗粒为研究对象，辨析山楂配方颗粒“喷干粉-条带-颗粒”关键属性及传递关系。方法 对影响山楂喷干粉、条带和颗粒性质的7个主要因素，进行部分因子试验，测定喷干粉、条带和颗粒的相关性质，经方差分析、多元线性回归以及正交偏最小二乘-判别分析（orthogonal partial least squares-discriminant analysis，OPLS-DA）进行建模与属性辨识。结果 辅料用量、进风温度和辊轮压力为山楂配方颗粒制备工艺的关键参数；试验辨析出以玻璃化转变温度（glass transition temperature，T_g）、粒径D₅₀为核心，与喷干粉含水量（H₁）、喷干粉堆密度（ρ_b1）和振实密度（ρ_t1）、条带得率和颗粒得率为辅的关键属性传递关系；其中T_g为代表性的、具有辨析和传递性的关键指标。结论 明确了山楂配方颗粒干法制粒过程中关键属性的辨析与传递关系，为质量控制策略及推动配方颗粒产业的高质量发展提供了依据。

Objective This study applied the quality by design (QbD) principle to identify key attributes and elucidate their transfer relationships along the “spray-dried powder-ribbon-granule” manufacturing chain of Shanzha (Crataegi Fructus) formula granules. Methods A fractional factorial design was implemented to investigate seven major factors affecting the properties of the spray-dried powder, ribbons, and granules. The relevant properties of these intermediates were measured. Modeling and attribute identification were performed using analysis of variance, multiple linear regression, and orthogonal partial least squares-discriminant analysis (OPLS-DA). Results Excipient amount, inlet air temperature, and roller pressure were identified as critical process parameters. A key attribute transfer relationship was established, centered on glass transition temperature (T_g) and median particle size (D₅₀), and associated with supporting attributes including moisture content (H₁), bulk density (ρ_b1), tapped density (ρ_t1) of the spray-dried powder, ribbon yield, and granule yield. Among these, T_g served as a representative key indicator with both discriminative and transfer functions. Conclusion This research clarifies the identification and transfer relationships of key attributes in the dry granulation process of Crataegi Fructus formula granules, providing a basis for developing effective quality control strategies and supporting the high-quality development of the formula granules industry.

R283.6

国家药品监督管理局药物制剂技术研究与评价重点实验室开放项目（2023TREDP01）；江西省重点研发计划项目（20212BBG71007）