Division of Product Quality Research, OTR/OPS, Food and Drug Administration, Silver Spring, Maryland 20993, USA.
J Pharm Sci. 2013 May;102(5):1513-23. doi: 10.1002/jps.23488. Epub 2013 Feb 28.
Various adverse events including esophagus irritations have been reported with the use of alendronate tablets, likely attributed to the rapid tablet disintegration in the mouth or esophagus. Accordingly, the disintegration of six alendronate tablet drug products was studied using a newly developed testing device equipped with in-line sensors, in addition to the official compendial procedure for measuring the disintegration time. The in-line sensors were used to monitor the particle count and solution pH change to assess the onset and duration of disintegration. A relatively large variation was observed in the disintegration time of the tested drug products using the compendial method. The data collected using the in-line sensors suggested that all tested drug products exhibited almost instantaneous onset of disintegration, under 2 s, and a sharp drop in solution pH. The drop in pH was slower for tablets with slower disintegration. The in-house prepared alendronate test tablets also showed similar trends suggesting rapid solubilization of the drug contributed to the fast tablet disintegration. This research highlights the usefulness of the newly developed in-line analytical method in combination with the compendial method in providing a better understanding of the disintegration and the accompanying drug solubilization processes for fast disintegrating tablet drug products.
各种不良反应事件，包括食管刺激，已被报道与使用阿伦膦酸钠片有关，可能归因于片剂在口腔或食管内迅速崩解。因此，使用新开发的配备在线传感器的测试设备研究了六种阿伦膦酸钠片药物产品的崩解情况，除了官方药典程序用于测量崩解时间。在线传感器用于监测颗粒计数和溶液 pH 值变化，以评估崩解的开始和持续时间。使用药典方法观察到测试药物产品的崩解时间存在较大差异。使用在线传感器收集的数据表明，所有测试药物产品均表现出几乎瞬间的崩解开始，在 2 秒内，溶液 pH 值急剧下降。崩解较慢的片剂 pH 值下降较慢。自制的阿伦膦酸钠测试片剂也表现出相似的趋势，表明药物的快速溶解有助于片剂的快速崩解。这项研究强调了新开发的在线分析方法与药典方法相结合的有用性，为快速崩解片剂药物产品的崩解和伴随的药物溶解过程提供了更好的理解。
