Gao Zongming, Smith Anjanette
Food and Drug Administration, Center for Drug Evaluation and Research, Division of Complex Drug Analysis, St. Louis, Missouri, 63110, USA.
Food and Drug Administration, Center for Drug Evaluation and Research, Division of Pharmaceutical Analysis, St. Louis, Missouri, 63110, USA.
AAPS J. 2023 Apr 26;25(3):46. doi: 10.1208/s12248-023-00813-6.
In vitro dissolution tests are widely used as quality control tools for drug products in development and manufacturing. Dissolution acceptance criteria are one of the important factors assessed during the regulatory review process. Understanding potential sources of variability is critical and a key to assuring reliable results are obtained when using a standardized system for in vitro dissolution testing. Sampling cannulas are commonly used to withdraw sample aliquots from dissolution medium and are potentially one of the testing factors that can contribute to variabilities in dissolution testing. However, there are still no clear requirements on the size or setting (intermittent or stationary) of sampling cannulas for dissolution testing. Thus, the objective of this study is to evaluate whether various sizes and sampling cannula settings yield different dissolution results using the USP 2 apparatus. Sampling cannulas with outer diameter (OD) ranging from 1.6 mm to 9.0 mm were used in dissolution testing with either intermittent or stationary setting to collect sample aliquots at multiple time points. The dissolution results at each time point were statistically analyzed for effects of both OD and setting of sampling cannula on drug release from 10 mg prednisone disintegrating tablets. Dissolution results indicated both size and setting of the sampling cannula may cause significant systematic errors, even though the dissolution apparatus has been calibrated. The degree of interference in dissolution results was directly related to the OD of the sampling cannula. Size of sampling cannula and setting of sampling procedure should be documented in standard operating procedures (SOP) for dissolution testing during method development.
体外溶出度试验被广泛用作药物研发和生产过程中的质量控制工具。溶出度验收标准是监管审评过程中评估的重要因素之一。了解潜在的变异性来源至关重要，并且是确保在使用标准化体外溶出度测试系统时获得可靠结果的关键。采样插管通常用于从溶出介质中抽取等分试样，并且可能是导致溶出度测试变异性的测试因素之一。然而，对于溶出度测试中采样插管的尺寸或设置（间歇式或固定式）仍没有明确要求。因此，本研究的目的是评估使用美国药典2型装置时，不同尺寸和采样插管设置是否会产生不同的溶出结果。外径范围为1.6毫米至9.0毫米的采样插管用于溶出度测试，采用间歇式或固定式设置，在多个时间点收集等分试样。对每个时间点的溶出结果进行统计分析，以研究采样插管的外径和设置对10毫克泼尼松分散片药物释放的影响。溶出结果表明，即使溶出度装置已经校准，采样插管的尺寸和设置仍可能导致显著的系统误差。溶出结果的干扰程度与采样插管的外径直接相关。在方法开发过程中，采样插管的尺寸和采样程序的设置应记录在溶出度测试的标准操作规程（SOP）中。
