Quality by design case study: An integrated multivariate approach to drug product and process development
Quality by design case study: An integrated multivariate approach to drug product and process development
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DOI：
10.1016/j.ijpharm.2009.07.031
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发表时间：
2009-12-01
影响因子：
5.8
通讯作者：
Nagi, Arwinder
中科院分区：
文献类型：
--
作者：
Huang, Jun;Kaul, Goldi;Nagi, Arwinder
为了促进深入的工艺理解，并提供制定控制策略以确保产品质量的机会，将实验设计、优化和多变量技术结合到药品的工艺开发中。过程 DOE 用于评估设计因素对可制造性和最终产品 CQA 的影响，并建立设计空间以确保所需的 CQA。为了提取最大信息，进行了两种类型的分析：DOE 效应和响应面分析以及多变量分析（PCA 和 PLS）。 DOE 效应分析用于评估三个设计因素（水量、湿重时间和润滑时间）对响应变量（混合流动、可压缩性和片剂溶出度）的相互作用和影响。设计空间是通过结合使用 DOE、优化和多变量分析来建立的，以确保获得所需的 CQA。对 DOE 批次的所有变量进行多变量分析，以研究变量之间的关系，并评估材料属性/工艺参数对可制造性和最终产品 CQA 的影响。集成的多变量方法例证了 QbD 原则和工具在药品和工艺开发中的应用。 (C) 2009 Elsevier B.V. 保留所有权利。
To facilitate an in-depth process understanding, and offer opportunities for developing control strategies to ensure product quality, a combination of experimental design, optimization and multivariate techniques was integrated into the process development of a drug product. A process DOE was used to evaluate effects of the design factors on manufacturability and final product CQAs, and establish design space to ensure desired CQAs. Two types of analyses were performed to extract maximal information, DOE effect & response surface analysis and multivariate analysis (PCA and PLS). The DOE effect analysis was used to evaluate the interactions and effects of three design factors (water amount, wet massing time and lubrication time), on response variables (blend flow, compressibility and tablet dissolution). The design space was established by the combined use of DOE, optimization and multivariate analysis to ensure desired CQAs. Multivariate analysis of all variables from the DOE batches was conducted to study relationships between the variables and to evaluate the impact of material attributes/process parameters on manufacturability and final product CQAs. The integrated multivariate approach exemplifies application of QbD principles and tools to drug product and process development. (C) 2009 Elsevier B.V. All rights reserved.