Qureshi S A, McGilveray I J
Therapeutic Products Directorate, Health Protection Branch (PL # 2202C1), Health Canada, Tunney's Pasture, Ottawa, Ontario K1A 0L2, Canada.
Eur J Pharm Sci. 1999 Feb;7(3):249-58. doi: 10.1016/s0928-0987(98)00034-7.
To evaluate variability in drug dissolution testing 28 laboratories analyzed USP calibrators, US FDA prednisone tablets and a marketed glibenclamide tablet product. The experiments were conducted using paddle and basket methods at 50 (calibrators) and 75 (glibenclamide) rpm. The media employed were deaerated by equilibrating at 37 degrees C for 24 h and by the USP recommended method. The 95% CI values for percent drug release for the USP calibrator tablets were similar to the reported tolerances for the USP Acceptance Ranges; however, individual results from 15 of 28 laboratories suggest that the apparatus would not comply with the USP Apparatus Suitability Criteria. For FDA prednisone calibrator tablets, percent drug release using equilibrated medium was different (P=0.003) than by the USP recommended method. For the glibenclamide tablet results, a CV of 14-37% was observed, depending upon the sampling time and the type of apparatus employed. The results indicate that failure to meet the USP Dissolution Apparatus Suitability Test may not truly mean that the apparatus is 'out of compliance'. Due to the high variability in dissolution testing, in many cases the impact of formulation or manufacturing changes on drug release characteristics may not be observed, in particular with multi-point profiles.
为评估药物溶出度测试中的变异性，28个实验室分析了美国药典（USP）校准品、美国食品药品监督管理局（FDA）的泼尼松片以及一种市售的格列本脲片产品。实验采用桨法和篮法，转速分别为50转/分钟（校准品）和75转/分钟（格列本脲）。所用介质通过在37℃平衡24小时以及采用USP推荐的方法进行脱气。USP校准片片剂的药物释放百分比的95%置信区间值与USP验收范围报告的公差相似；然而，28个实验室中有15个实验室的个别结果表明该仪器不符合USP仪器适用性标准。对于FDA泼尼松校准片片剂，使用平衡介质的药物释放百分比与USP推荐方法不同（P = 0.003）。对于格列本脲片的结果，观察到的变异系数为14% - 37%，这取决于取样时间和所用仪器类型。结果表明，未能通过USP溶出度仪器适用性测试可能并不真的意味着仪器“不符合规定”。由于溶出度测试中的高变异性，在许多情况下，可能观察不到制剂或生产变化对药物释放特性的影响，尤其是对于多点曲线。
