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编号: 13000941
质量源于设计在银杏叶片制粒工艺中的应用(Ⅳ):原料质量波动的影响及控制(1)
//www.caroetjl.com 2017年3月15日 《中国中药杂志》 2017年第6期
[摘要]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(D50)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、D10、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。

[关键词]关键物料属性; 质量一致性; 银杏叶片; 模式地图; 扭矩曲线
, 百拇医药
[Abstract]Raw materials′ quality variation could affect the quality consistency of product and the clinical efficacy In this paper, the high shear wet granulation (HSWG) process of the ginkgo leaf tablet was taken as the research object Ginkgo biloba extracts and excipients microcrystalline cellulose collected from various sources and batches were used to simulate raw materials′ quality variation Realtime torque was recorded to analyze the viscosity of the wetting mass, and then by combining with physical fingerprint, the impact of physical quality variation of powders on granule properties could be investigated Based on regime map thesis, whether the granules′ nucleation mode was in mechanical dispersion regime was determined by calculating dimensionless parameters, which would lead to the unstable output in considerations of granule yield ratio and particle size distribution (PSD) curve The orthogonal partial least square (OPLS) model was adopted to build the relationship between the micromeritic properties and the mediangranule size (D50) of Ginkgo biloba granules and then the critical material attributes (CMAs) were screened by variable importance in the projection (VIP) indexes The results demonstrated that the properties of powders including hygroscopicity, angle of repose, Hausner ratio, Carr index, D10 and loss on drying affected the granule size Besides, Ginkgo biloba granules were compressed into tablets In view of tensile strength analysis, the raw materials′ quality variation did not result in decrease of tensile strength of the ginkgo leaf tablets The design space of critical quality attributes (CQAs) and the process design space which could cope with raw materials′ quality variation were proved to be robust

[Key words]critical material attributes; quality consistency; ginkgo leaf tablet; regime map; torque curve

質量源于设计(quality by design,QbD)[12]理念强调对过程透彻的理解,通过对原料、工艺过程、以及产品质量之间关系的系统研究,来提高过程的可控性。其中,原料质量属性研究是系统QbD研究的重要组成部分,科学的产品工艺设计需理解原料的物理、化学、生物、生物药剂性质对产品质量的影响。通过建立原料质量控制标准和工艺设计空间,使产品关键质量属性(critical quality attributes,CQA)符合预期目标。 , //www.caroetjl.com (崔向龙 徐冰 刘俊文 石国琳 史新元 乔延江)
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