| 引用本文:罗赣1，徐冰1，孙飞2，马群1，史新元1，乔延江1.中药质量源于设计方法和应用：工艺放大[J].世界中医药,2018,(03):. |
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| 中药质量源于设计方法和应用：工艺放大 |
| Chinese Medicine Quality Derived From Design Methods and Applications for-(Ⅳ)：Process Scale-up |
| 投稿时间：2017-12-13 |
| DOI：10.3969/j.issn.1673-7202.2018.03.002 |
| 中文关键词: 质量源于设计 工艺放大 动态设计空间 高速剪切湿法制粒过程 模式地图 |
| English Keywords:Quality by design Process scale-up Dynamic design space High shear wet granulation process Regime map |
| 基金项目:国家中药标准化项目（ZYBZH-C-QIN-45）；国家自然科学基金项目（81403112）;国家自然科学基金重点项目（81430094） |
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| 中文摘要: |
| 当制药工艺从实验室小试规模向生产规模放大时，工艺规模成为影响产品质量的新的变量。小试规模下工艺参数对产品质量的影响在中试规模或生产规模下可能呈现另外情况。在质量源于设计（QbD）框架下，加入工艺规模这个新的变量，势必对制药过程的理解提出了更高要求。本文总结了常用制药工艺放大的方法，并重点介绍了数学模拟放大。以高速剪切湿法制粒过程为例，通过采用量纲分析，保持各规模间颗粒增长微环境的动力学和热力学相似，建立非规模依赖型工艺动态设计空间，扩展了设计空间的边界和范围，提高了工艺对变化因素的容忍性，产品可变性得到有效控制。 |
| English Summary: |
| When a pharmaceutical process was transferred from lab to industry, the process scale became a new variable which had impacts on the product quality. Under the framework of pharmaceutical quality by design (QbD), the addition of process scale as a new variable need further understandings of pharmaceutical processes. This paper summarized common methods for pharmaceutical scale-up study. In particular, mathematical modeling and simulation based scale-up methods were introduced in detail. The high shear wet granulation process was selected as an example. Dimensionless analysis was performed to maintain the similar dynamics and thermodynamics of micro environment of particle growth at different scales. And then process dynamic design space was built and was dimension independent. The boundary and range of process design space were extended. The tolerance of process for changeable variables was improved and quality variability of the product was well controlled. |
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