流通池法测定曲安奈德益康唑乳膏释放度的方法研究  

Dissolution study of triamcinolone acetonide and econazole nitrate cream by a flowthrough cell method

作　　者：沈丹丹 张伟 罗立骏 孙涪陵 侯立新 Shen Dan-dan;Zhang Wei;Luo Li-jun;Sun Fu-ling;Hou Li-xin(Institute for Food and Drug Control,Chongqing,NMPA Key Laboratory of Quality Monitoring of Anesthetic and Psychotropic Substances,Chongqing 401121;Chongqing Rennzar Pharmaceutical Technology Co.,Ltd,Chongqing 400021)

机构地区：[1]重庆市食品药品检验检测研究院,国家药品监督管理局麻醉精神药品质量监测重点实验室,重庆401121 [2]重庆仁泽医药科技有限公司,重庆400021

出　　处：《中国抗生素杂志》2023年第2期201-208,共8页Chinese Journal of Antibiotics

基　　金：重庆市科研机构绩效引导专项(No.cstc2019jxj130034)。

摘　　要：目的建立流通池测定曲安奈德益康唑乳膏两个活性成分的释放度方法。方法采用流通池法闭合系统装置测定曲安奈德益康唑乳膏的释放度,分别考察释放介质、放置方式、流速及半透膜孔径对两个活性成分体外释放曲线的影响,比较两个生产企业市售产品体外释放行为的差异;以HPLC测定释放量,采用Luna C_(8)柱(250 mm×4.6 mm,5μm),梯度洗脱,检测波长227 nm,柱温40℃,流速1.0 mL/min,进样量100μL。结果以含0.05%十二烷基硫酸钠的0.9%氯化钠溶液为释放介质,温度为(32±0.5)℃,流速为16 mL/min,半固体适配器半透膜孔径为2.7μm,过滤装置为0.45μm混合纤维素膜,可以获得既能有效释放又具有一定区分力的释放曲线。曲安奈德在浓度0.0052~0.7803μg/mL范围内线性良好(r=0.9994),硝酸益康唑在浓度0.0552~8.2851μg/mL范围内线性良好(r=0.9993)。两个生产企业的体外释放曲线存在显著性差异,活性成分粒度可能是影响释放行为差异的主要因素之一。结论该方法准确度好、灵敏度高,可用于曲安奈德益康唑乳膏的释放度检查,对优化处方及生产工艺具有重要意义,并有利于推动企业一致性评价工作。Objective To develop a flow-through cell method for the determination of the dissolution of two active ingredients of triamcinolone acetonide and econazole nitrate cream.Methods The flow-through cell method with closed system device was conducted to determine the dissolution of triamcinolone acetonide and econazole nitrate cream.The effects of the release medium,placement method,flow rate,and semi-permeable membrane diameter on the in vitro release curves of the two active ingredients were investigated.Differences in the release behavior in vitro of two commercial products were compared.An HPLC method was employed to determine the content of triamcinolone acetonide and econazole nitrate on a column of Luna C_(8)(250 mm×4.6 mm,5μm)with gradient elution,the detection wavelength was set at 227 nm,the column temperature was 40℃,the flow rate was 1.0 mL/min,and the injection volume was 100μL.Results The dissolution curve with a suitable degree of distinction can be obtained by using 0.9%sodium chloride solution containing 0.05%sodium dodecyl sulfate as the dissolution medium,at the flow rate of 16 mL/min,the temperature was 32℃±0.5℃,the diameter of semi-permeable membrane was 2.7μm,and the mixed cellulose film of 0.45μm was used as the filter device.There was good linear relationship between the concentration and peak area in the range of 0.0052~0.7803μg/mL for triamcinolone acetonide(r=0.9994)and 0.0552~8.2851μg/mL for econazole nitrate(r=0.9993).There was significant difference in the in vitro release curves of the two manufacturers,and the particle size of the active ingredient might be one of the main factors affecting the release behavior.Conclusion The accurate and sensitive approach can be used for determination of the dissolution of triamcinolone acetonide and econazole nitrate cream,which is of major importance of optimizing formulations and production processes,and is beneficial to promote consistency evaluation for manufacturers.

关 键 词：曲安奈德益康唑乳膏 流通池法 释放度 HPLC 一致性评价 

分 类 号：R9[医药卫生—药学]