Validation of Dissolution Testing with Biorelevant Media: An OrBiTo Study
Validation of Dissolution Testing with Biorelevant Media: An OrBiTo Study
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DOI：
10.1021/acs.molpharmaceut.7b00198
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发表时间：
2017-12-01
影响因子：
4.9
通讯作者：
Butler, James
中科院分区：
文献类型：
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作者：
Mann, James;Dressman, Jennifer;Butler, James
作为一种更好地了解药物和制剂在胃肠道中行为的手段，生物悬浮介质的溶出度测试在制药行业中已变得普遍。然而，到目前为止，很少有人试图衡量用这些方法获得的结果的重复性。这项研究的目的是确定使用PATLE仪器(USP2)进行生物悬浮剂溶出度测试的实验室间重复性。13个工业实验室和3个学术实验室参与了这项研究。所有实验室都提供了进行试验的标准方案：在FaSSGF中释放模拟在胃中释放，在单一肠道介质中释放，FaSSIF模拟在小肠中释放，以及当条件从胃环境改变到肠道环境时模拟浓度分布的“转移”(两阶段)方案。选择的测试产品是市面上出售的布洛芬片和扎鲁司特片。生物悬浮剂溶出度试验表明，尽管使用了几个不同批次的商用介质制剂粉末，但参与实验室之间的重复性很高。同样，商业生物悬浮培养基和内部生产的结果几乎相同。将结果与以前的环状研究结果进行比较，包括在单一介质中使用USP校准剂片剂或商业可得医药产品进行的研究，生物悬浮剂研究的结果在实验室间具有高度的重复性。两阶段试验的实验室间重复性也是可以接受的，尽管变异性比单一介质试验稍大一些。生物悬浮剂溶出度测试在实验室之间重复性很高，可用于实验室间的比较。
Dissolution testing with biorelevant media has become widespread in the pharmaceutical industry as a means of better understanding how drugs and formulations behave in the gastrointestinal tract. Until now, however, there have been few attempts to gauge the reproducibility of results obtained with these methods. The aim of this study was to determine the interlaboratory reproducibility of biorelevant dissolution testing, using the paddle apparatus (USP 2). Thirteen industrial and three academic laboratories participated in this study. All laboratories were provided with standard protocols for running the tests: dissolution in FaSSGF to simulate release in the stomach, dissolution in a single intestinal medium, FaSSIF, to simulate release in the small intestine, and a "transfer" (two-stage) protocol to simulate the concentration profile when conditions are changed from the gastric to the intestinal environment. The test products chosen were commercially available ibuprofen tablets and zafirlukast tablets. The biorelevant dissolution tests showed a high degree of reproducibility among the participating laboratories, even though several different batches of the commercially available medium preparation powder were used. Likewise, results were almost identical between the commercial biorelevant media and those produced in-house. Comparing results to previous ring studies, including those performed with USP calibrator tablets or commercially available pharmaceutical products in a single medium, the results for the biorelevant studies were highly reproducible on an interlaboratory basis. Interlaboratory reproducibility with the two-stage test was also acceptable, although the variability was somewhat greater than with the single medium tests. Biorelevant dissolution testing is highly reproducible among laboratories and can be relied upon for cross-laboratory comparisons.