复方倍他米松注射混悬液溶出度方法的开发和验证  

Development and validation of dissolution test for betamethasone injectable suspension

作　　者：沈丹丹 吴群 张涛 

机构地区：[1]重庆市食品药品检验检测研究院,重庆401121 [2]重庆市药物过程与质量控制工程技术研究中心,重庆401121 [3]福安药业集团重庆礼邦药物开发有限公司,重庆401121

出　　处：《中国新药杂志》2017年第14期1712-1717,共6页Chinese Journal of New Drugs

摘　　要：目的:建立复方倍他米松注射液中缓释活性药用成分二丙酸倍他米松的溶出度测定方法。方法:采用Agilent ZORBAX SB-C18柱(150 mm×4.6 mm,5μm),以甲醇-乙腈-0.01 mol·L^(-1)磷酸二氢铵(34∶32∶34)为流动相,检测波长242 nm,柱温35℃,流速1.0 m L·min^(-1)。筛选含不同表面活性剂浓度的pH 7.4磷酸钠缓冲液、pH 7.4模拟体液、pH 7.0模拟肌液、pH 7.4模拟关节液的溶出介质,测定本品中二丙酸倍他米松体外溶出曲线,溶出方法为桨法,转速50 r·min^(-1)。结果:二丙酸倍他米松在浓度0.209 8~13.989 4μg·m L^(-1)范围内与峰面积呈良好线性关系,平均回收率(n=9)为100.15%(RSD=1.1%)。以选择含0.05%十二烷基硫酸钠的pH 7.4磷酸钠缓冲液为溶出介质时,能获得具有适当区分度的溶出曲线。二丙酸倍他米松在4种溶出介质中溶出行为无明显差异。结论:该方法简单、准确,可用于复方倍他米松注射液溶出度的测定,有利于提高本品的质量可控性。Objective： To develop a method for determination of the dissolution of sustained release betamethasone dipropionate injectable suspension. Methods： An Agilent ZORBAX SB-CIs column （150 mm× 4.6 mm,5 μm） was used. The mobile phase was methanol-acetonitrile-0.01 mol· L-1 ammonium dihydrogen phosphate （34：32：34）, the flow rate was 1.0 mL-min-1, the detection wavelength was set at 242 nm, and the column temperature was 35℃. The dissolution medium was screened among pH 7.4 sodium phosphate buffer, pH 7.4 simulated body fluid, pH 7. 0 simulated muscular fluid and pH 7. 4 simulated synovia] fluid, each containing different concentrations of surfactant. The dissolution profiles were studied by the paddle apparatus, with stirring speed of 50 r.min-1 Results： There was a good linear relationship between the concentration and peak area in the range of 0. 209 8 - 13. 989 4 ~g. mL ~ for betamethasone dipropionate ; the average recovery （ n = 9 ） was 100.15 % （RSD = 1. 1% ）. The dissolution curve with a suitable degree of distinction could be obtained by using pH 7.4 sodium phosphate buffer containing 0.05% sodium dodecyl sulfate as dissolution medium. The dissolution behavior of betamethasone dipropionate measured in different dissolution media had no significant difference. Conclusion： The method is simple and accurate. It can be used for determination of the dissolution of betamethasone dipropionate injectable suspension, is beneficial to improve the quality controllability of the product

关 键 词：复方倍他米松注射液 高效液相色谱法 溶出度 

分 类 号：R927.11[医药卫生—药学]