As a result of the excipient materials added to the drug substance to create a formulated pharmaceutical product, the preparation of drug product samples for chromatographic or other quantitative analysis can be manually intensive and time-consuming. It is therefore important that enough focus is placed on this aspect of method development to ensure accurate and reproducible results are obtainable across different laboratories. This paper outlines some of the challenges encountered when developing quantitative assay methods which are attributable to sample preparation procedures for solid-oral dosage forms (i.e. tablets and capsules). Approaches utilising experimental design, data visualisation and process understanding tools are described to highlight the importance of common sample preparation factors on drug recovery in product formulations. For a tablet formulation, experimental design highlighted that the percentage of organic in the sample diluent and the orbital shaker speed were statistically significant and could impact accuracy of assay result. For the second formulation, a gelatin capsule, the use of experimental design and the Britest process understanding tools highlighted the initial volumetric flask fill volume required close control to ensure reproducible assay results while the stand time (time sample left to stand post-shaking to aid analyte solubilisation) and capsule storage conditions were also significant.

中文翻译：

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使用实验设计和过程理解工具提高药物剂型样品制备的稳健性

由于将赋形剂材料添加到药物物质中以创建配制的药物产品，因此用于色谱或其他定量分析的药物产品样品的制备可能需要大量人工且耗时。因此，对方法开发的这一方面给予足够的关注以确保在不同的实验室中获得准确和可重复的结果非常重要。本文概述了在开发定量分析方法时遇到的一些挑战，这些挑战归因于固体口服剂型（即片剂和胶囊）的样品制备程序。描述了利用实验设计、数据可视化和过程理解工具的方法，以强调常见样品制备因素对产品配方中药物回收率的重要性。对于片剂配方，实验设计强调样品稀释剂中有机物的百分比和轨道摇床速度在统计上是显着的，并且会影响测定结果的准确性。对于第二种配方，明胶胶囊，实验设计和 Britest 过程理解工具的使用强调了初始容量瓶填充体积需要严格控制以确保可重复的测定结果，同时静置时间（样品在摇动后静置的时间以帮助分析物溶解）和胶囊储存条件也很重要。