利用QbD改善和保证卡托普利片空白颗粒法工艺放大的效益和最终产品的质量_new教程.doc

摘 要 关键词： 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 Abstract QbD, 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 the analysis and understanding of the Critical Quality Attributes and the process for the scale-up of the blank granulation method, the Critical Process Parameters for the?scale-up of the blank granulation process of captopril were identified, i.e., moisture?content of particles, and the prameters of granulation and final mix.? Third,?through applying?risk evaluation, DOE, and PAT technologies and methods, and?other available?knowledge and information, the function of the Critical Quality Attributes and?the Critial?Process Parameters was derived.? In turn, the design space of the scale-up of?blank granulation process was determined.? Lastly, the manufacturing of the product was conducted within the design space.? According?to the statistics of first time pass rate, all?Critical Quality Attributes?were within the internal control specifications, demonstrating?the improvement of the scale-up efficiency and the?ensurence of the final product?quality.??? Key Words: QbD,Captopril Tablets,Process Scale-up,Critical Product Attributes, Critical Process Parameters 目 录第一章 1.1 背景介绍……………