摘 要QbD 是质量源于设计（Quality by Design）的简称，是一种科学的、基于风险的、全面的和先进的药品开发方法，强调通过对产品属性和生产工艺的理解，通过设计和控制来保证产品的质量属性。本文运用 QbD 理念，以某生产企业为例，详细阐述了 QbD 在卡托普利片空白颗粒法工艺放大中的应用及作用。首先，根据产品目标特性，确定了卡托普利片的关键质量属性，为标示量、溶出度、卡托普利二硫化物、含量均匀度、硬度、脆碎度；其次，针对该部分关键质量属性及空白颗粒法工艺放大的工艺与过程进行分析、理解，并应用风险评估，确定了工艺放大的关键工艺参数，为颗粒水分、制粒参数、整粒参数、混合参数；第三，通过风险评估、实验设计、过程分析等技术手段和方法及现有知识，详细说明了关键质量属性及关键工艺参数间的函数关系，进而确定了卡托普利片空白颗粒法工艺放大的设计空间与控制策略。最后，在设计空间内进行生产操作，关键质量属性指标均控制在内控标准范围内，经统计产品一次合格率等指标，确认利用 QbD 可以改善和保证卡托普利片空白颗粒法工艺放大的效益及最终产品的质量。关键词： QbD；卡托普利片；工艺放大；关键质量属性；关键工艺参数Application of QbD in the Process Scale Up of the Blank Granulation Method in Captopril Tablet Manufacturing to Enhance and Ensure the Improvement of Efficiency and Final Product Quality AbstractQbD, the abbreviattion for "Quality by Design", is a scientific, risk-based holistic and proactive approach to pharmaceutical product development, which emphasizes on the understanding of product attributes and process control, and ensuring the quality attributes of a product through design and control.This thesis, with the manufacturing of captopril tablet as an exmaple, illustrated the application and beneficial effect of QbD in the scale-up of the blank granulation process.First, based on the target product profile, the Critical Quality Attributes of captopril tablet were confirmed, i.e., dissolution, captopril disulfide, content uniformity, strength, and friability. Second, through...
