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原料质量变异影响产品质量一致性和临床疗效。该文以银杏叶片高速剪切湿法制粒工艺(HSWG)为研究对象,收集不同厂家和批次的银杏叶提取物和辅料微晶纤维素,模拟原料波动。实时记录湿法制粒过程扭矩,分析湿软材黏着力。结合物理指纹图谱,考察原料粉末物理质量变异对颗粒中间体粉体学性质的影响。根据湿法制粒Regime map理论,通过无量纲参数计算,判断银杏叶片HSWG中颗粒的润湿与成核处于机械分散区,颗粒收率和颗粒粒径分布曲线表明该区域过程输出的不稳定性。采用正交偏最小二乘(OPLS)法建立18批原料粉末粉体学性质和和银杏叶颗粒中值粒径(D_(50))的关联模型,以变量投影重要性(VIP)筛选原料关键物料属性(CMAs)。结果表明原料粉末吸湿性、休止角、豪斯纳比、卡尔指数、D_(10)、干燥失重影响颗粒粒度。进一步将银杏叶颗粒压制成片,并测定片剂抗张强度,发现原料质量波动未导致片剂机械强度的降低,银杏叶颗粒关键质量属性设计空间和过程设计空间稳健可靠,可有效应对原料质量波动。
Variation of raw material quality affects product consistency and clinical efficacy. In this paper, high-speed shear wet granulation process (HSWG) of Ginkgo biloba leaves was taken as the research object. Ginkgo biloba extract and excipient microcrystalline cellulose from different factories and batches were collected to simulate the fluctuation of raw materials. Real-time recording wet granulation process torque, wet adhesive adhesion analysis. Combined with physical fingerprints, we investigated the effect of variation of physical quality of raw powder on the powder properties of granular intermediate. According to the wet granulation Regime map theory, the wetting and nucleation of particles in the HSWG of Ginkgo biloba leaves were judged to be in mechanical dispersion by the dimensionless parameter calculation. The particle yield and particle size distribution curve showed that the process output instability in this region. The orthogonal model was established by Orthogonal Partial Least Squares (OPLS) method to establish the correlation model between the powdery properties of 18 batches of raw materials and the median diameter of grains of Ginkgo biloba (D_ (50)). Material Properties (CMAs). The results show that the moisture absorption, angle of repose, Hausner’s ratio, Karl’s index, D_ (10), weight loss on drying affect the particle size. Ginkgo biloba leaf particles were further compressed into tablets, and the tablet tensile strength was measured. It was found that the fluctuation of raw material quality did not lead to the decrease of the mechanical strength of tablets. The design space and process design space of key quality attributes of Ginkgo biloba leaves were stable and reliable, fluctuation.