利巴韦林胶囊溶出曲线测定方法的建立及国产利巴韦林胶囊溶出行为的考察

Establishment of dissolution curves test method of Ribavirin capsules and investigation with domestic ribavirin capsules of dissolution behavior

目的建立利巴韦林胶囊溶出曲线测定方法,考察国内利巴韦林胶囊溶出行为,为该品种仿制药质量一致性评价工作提供实验依据。方法采用《中国药典》2010年版（二部）附录ⅩC第一法（篮法）,转速50 r/min,分别以p H 1.2盐酸溶液、p H 4.5醋酸盐缓冲液、p H 6.8磷酸盐缓冲液、水为溶出介质,溶出介质体积900 m L,于不同时间点取样测定并绘制4种溶出介质下的溶出曲线。采用高效液相色谱法进行溶出度测定。色谱柱为C18柱,流动相为4 g/L的磷酸二氢钠溶液（用5%氢氧化钠溶液调节p H至5.0±0.05）-乙腈（98︰2）,流速为1.0 m L/min,检测波长为225 nm,进样量为10μL。结果利巴韦林供试品溶液浓度在2.5~200μg/m L范围内与峰面积呈良好的线性关系（r=1）;精密度、稳定性试验的RSD≤0.5%,4种溶出介质中平均回收率分别为101.3%、100.7%、100.2%和100.4%。p H4.5和p H6.8溶出介质中各企业胶囊溶出行为比较一致并可以迅速溶出,p H1.2和水溶出介质中溶出行为差异较大,且有部分企业不能达到15 min的平均溶出量大于85%。结论建立的溶出曲线测定方法准确、可靠。国产利巴韦林胶囊之间溶出行为存在差异,其制剂工艺水平还有提升的空间。

Objective To establish the dissolution curves test method of Ribavirin capsules,and investigate dissolution behavior of domestic Ribavirin capsules. To provide experimental basis for generic drugs quality consistency evaluation. Methods According to the first dissolution method（ basket method） stated in appendix Ⅹof Chinese Pharmacopeia（ 2010 edition）,the rotation speed was 50 r/min with dissolution medium volume of 900 m L. The dissolution profiles of Ribavirin capsules in four different mediums（ p H 1. 2 hydrochloric acid solution,p H 4. 5 acetic buffer,p H 6. 8 phosphate buffer and water） were determined by HPLC. The determination was performed on C18 column with mobile phase consisted of 4 g / L sodium dihydrogen phosphate solution（ p H adjusted to 5. 0 ± 0. 05 using 5% sodium hydroxide solution）-acetonitrile（ 98∶2） at the flow rate of 1. 0 m L / min. The detection wavelength was 225 nm,and sample size was 10 μL. Results The linear range of ribavirin was 2. 5-200 μg / m L（ r = 1）. RSD of precision and stability tests were lower than 0. 5%. The average recoveries were 101. 3%,100. 7%,100. 2%,100. 4% in four mediums. Dissolution behavior of capsules can be more consistent and rapid dissolution in p H4. 5 and p H6. 8 mediums. But they were quite different in p H1. 2 and water mediums,and some of their average dissolution at 15 min could not reach 85%. Conclusion This method is accurate and reliable. There is a difference between domestic Ribavirin capsules dissolution behavior,and the formulation processes have room for improvement.