摘要
目的：比较国产马来酸依那普利片与国外原研药在4种不同pH的溶出介质中的溶出曲线,为仿制药质量一致性评价工作的开展和该制剂生产工艺的提高提供参考。方法：采用高效液相色谱法进行溶出度测定。色谱柱为Agilent Zorbax Eclipse XDB-C8,流动相为0.01 mol/L磷酸二氢钾溶液（用磷酸调pH至2.2）-乙腈（75∶25,V/V）,流速为1.0 ml/min,检测波长为215nm,进样量为50μl,柱温为50℃。采用《中国药典》2010年版（二部）附录ⅩC第二法（桨法）,转速50 r/min,分别以pH 1.0盐酸溶液、pH 4.5磷酸盐缓冲液、pH 6.8磷酸盐缓冲液、水为溶出介质,溶出介质体积900 ml,于不同时点取样测定并绘制4种样品的溶出曲线,并采用f2相似因子法来考察其相似性。结果：马来酸依那普利检测质量浓度在1.0~20μg/ml范围内与峰面积积分值呈良好的线性关系（0.999 9）;精密度、稳定性试验的RSD≤0.66%;4种介质中的平均回收率分别为99.1%、99.1%、99.9%、100.2%,RSD分别为1.0%、0.7%、0.7%、0.6%（n=9）。国外原研药在4种溶出介质中的溶出曲线基本一致;但所测定国产马来酸依那普利片在4种溶出介质中的溶出曲线,仅有1家企业产品与原研药溶出曲线具有相似性。结论：国内外不同厂家的马来酸依那普利片在4种溶出介质中的溶出曲线存在差异,有必要加强对其多pH溶出曲线的实时监控,确保药品质量的有效性、均一性和稳定性。
OBJECTIVE： To compare the dissolution curves of domestic Enalaprilmaleate tablets and foreign original drug in 4 kinds of mediums, and to provide reference for generic drugs quality consistency evaluation and the improvement of production technology. METHODS： HPLC method was adopted. The determination was performed on Agilent Zorbax Eclipse XDB-C8 column with mobile phase consisted of 0.01 mol/L monopotassium phosphate solution （pH adjusted to 2.2 using phosphoric acid）-acetonitrile （75 ： 25, V/V） at the flow rate of 1.0 ml/min. The detection wavelength was set at 215 nm, and sample size was 50μl. The column temperature was 50℃.According to the second dissolution method （paddle method） stated in appendix X of Chinese Pharmacopeia （2010 edition）, the rotation speed was 50 r/min with dissolution medium volume of 900 ml. The dissolution profiles of 4 kinds of Enalaprilmaleate tablets in 4 different mediums （pill.0 hydrochloric acid solution, pH4.5 phosphate buffer, pHr.8 phosphate buffer and water） were determined by HPLC. The similarity was investigated by similarity factors （f2）. RESULTS： The linear range of enalaprilmaleate were 1.0-20μg/ml （r=0.999 9）. RSDs of precision and stability tests were lower than 0.66%. Average recoveries were 99.1% （RSD=I.0%, n=9）, 99.1% （RSD=0.7%, n=9）, 99.9% （RSD=0.7%, n=9） and 100.2% （RSD= 0.6%, n=9） in 4 mediums, respectively. The dissolution curves of foreign original drugs were similar in 4 kinds of medium. But only one of the dissolution curves of domestic Enalaprilmaleate tablets in 4 different mediums was similar to original drugs. CONCLUSIONS： There are important differences in the dissolution curves of domestic and foreign Enalaprilmaleate tablets in 4 different mediums. It is necessary to strengthen monitoring of dissolution profiles, to ensure effectiveness, homogeneous and stability of drug quality.
出处
《中国药房》
CAS
CSCD
2014年第32期3053-3056,共4页
China Pharmacy
