环境湿度对硫酸氢氯吡格雷片溶出度的影响

Effect of ambient humidity on dissolution of clopidogrel Bisulfate tablets

关键词:  硫酸氢氯吡格雷片  溶出  交联聚维酮  湿度  动态水分吸附分析

Key words:  clopidogrel bisulfate tablets  dissolution  crospovidone  humidity  dynamic vapour absorption analysis

摘要:

目的 考察2种处方的硫酸氢氯吡格雷片在(75±5)%相对湿度(relative humidity，RH)条件下放置时长对溶出速率的影响，为药物溶出曲线检测异常数据的调查提供参考。方法 将硫酸氢氯吡格雷片处方1和处方2的样品装入密闭的样品盒中，置于饱和氯化钠溶液模拟的75%RH的环境中放置1，2，3 h后检测溶出曲线和水分，并与未经吸湿样品的溶出曲线进行非模型依赖相似因子比较。结果 处方1的样品在(75±5)%RH下放置2 h后即与0 h不相似，而处方2的样品放置4 h后仍然相似。处方1制剂在3 h内水分增长比处方2制剂快，并且在5 h内持续增长，而处方2制剂在2 h后水分增长即变缓。结论 处方1中的崩解剂比处方2多了交联聚维酮，含有交联聚维酮的处方对环境的湿度变化比较敏感，因此对于此类制剂不管是在保存还是检测都应该考虑环境湿度的影响。

Abstract:

OBJECTIVE To investigate the effect of the duration of storage under (75±5)% relative humidity(RH) on the dissolution rate of two formulations of clopidogrel bisulfate tablets, providing reference for investigating abnormal data in the drug dissolution curve. METHODS Samples of preparation 1 and preparation 2 of clopidogrel bisulfate tablets were placed in sealed sample boxes and stored in an environment with 75% RH simulated by saturated sodium chloride for 1, 2, and 3 h. The dissolution curves and moisture content were measured and compared with the dissolution curves of samples without humidity absorption using a non-model dependent similarity factor. RESULTS Samples of preparation 1 were dissimilar to 0 h after 2 h of storage under (75±5)% RH, while samples of preparation 2 were still similar after 4 h of storage. Moisture content of the preparation 1 increased faster than that of preparation 2 within 3 h and continued to increase within 5 h, while moisture content of preparation 2 increased more slowly after 2 h. CONCLUSION Preparation 1 contains more crosslinked polyvinylpyrrolidone as a disintegrant than preparation 2, which makes it more sensitive to changes in environmental humidity. Therefore, the impact of environmental humidity should be considered for such formulations in both storage and testing.