Pozy Ethan J, Tian Li
Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Quality (OPQ), Office of Pharmaceutical Quality Research (OPQR), St Louis, Missouri 63110, USA.
Anal Methods. 2025 Mar 20;17(12):2559-2566. doi: 10.1039/d4ay02008a.
Dissolution testing is a method to assess the impact of pharmaceutical formulation and bioequivalence between comparator drugs, among other uses. The dissolution paddle tester (USP Apparatus 2) has been widely used by industry to evaluate the rate of a drug's dissolution from a formulation. The United States Pharmacopeia (USP) issued a new Dissolution Performance Verification Standard (DPVS) - Prednisone Reference Standard in 2023, along with a new set of Performance Verification Test (PVT) criteria to be performed in addition to mechanical calibration for instrument qualification. Apex vessels are dissolution vessels with a convex bottom that have gained interest due to improved hydrodynamics and reduced accumulation of trapped drug product in formulation at the bottom of the vessel during dissolution testing. In this study, we evaluated the effect of changing mechanical calibration parameters within the acceptable mechanical calibration ranges and their impacts on the dissolution of the new DPVS - Prednisone tablets in deaerated water using both standard and apex vessels as well as whether the test results from varied apparatus configurations met the PVT acceptance criteria. All configurations within specified parameters for standard vessels fell within PVT acceptance criteria, but the higher dissolution rate in apex vessels fell beyond the current PVT acceptance range. This indicates that the current PVT or DPVS-Prednisone tablet is not suitable for the qualification of USP Apparatus 2 fitted with apex vessels.
溶出度测试是一种评估药物制剂影响以及比较药物之间生物等效性等的方法。溶出桨法测试仪（美国药典装置2）已被制药行业广泛用于评估药物从制剂中的溶出速率。美国药典（USP）于2023年发布了新的溶出性能验证标准（DPVS）——泼尼松对照品，以及一套除机械校准外还需进行的性能验证测试（PVT）标准，用于仪器鉴定。Apex溶出杯是底部呈凸形的溶出杯，由于其在溶出测试过程中改善了流体动力学性能且减少了制剂中药物产品在杯底的滞留积累，因而受到关注。在本研究中，我们评估了在可接受的机械校准范围内改变机械校准参数的效果，以及它们对使用标准溶出杯和Apex溶出杯在脱气水中新DPVS - 泼尼松片剂溶出的影响，同时评估了不同仪器配置的测试结果是否符合PVT验收标准。标准溶出杯在指定参数内的所有配置均符合PVT验收标准，但Apex溶出杯中的较高溶出速率超出了当前PVT验收范围。这表明当前的PVT或DPVS - 泼尼松片剂不适用于配备Apex溶出杯的美国药典装置2的鉴定。
