醋酸曲安奈德益康唑乳膏透皮吸收试验

摘要

Objective To establish an HPLC method for quantitative determination of triamcinolone acetonide acetate and econazole nitrate in vitro percutaneous solution,and investigate the ability of percutaneous penetration of triamcinolone acetonide acetate and econazole nitrate cream. Methods Chromatographic column:C8(5 μm) (SP-120 -5 -C8 - AP) ;Mobile phase:gradient elution ;0.094% anhydr-sodium hexanesulfonate [ purification water - cyanide - isopropyl alcohol (720: 40: 40) ]( adjust the pH to 3 with 85% phosphoric acid) as mobile phase A, 0.094% sodium hexanesulfonate [ purification water - methanol ( 100: 900) ] ( adjust the pH to 3 with 85% phosphoric acid) as mobile phase B. Detection wavelength:227 nm. Flow rate:1.0 mL/min. Injection:20 . Improved Franz type diffusion cells were used in vitro permeation studies and excised minipigs skins in vitro were used as transdermal barrier. The concentration of triamcinolone acetonide acetate and econazole nitrate in the receptor solution was determined by HPLC to investigate its cumulative permeation quantities at different time respectively and compared with that of the commercial cream. Results The regression equation of triamcinolone econazole nitrate was linear in the range of 0.50μg/mL -4.00 μg/mL (4 = 0.8834 × C +0.05075 ,r =0.9991). The average recovery was all between 85% -115%. A good linear relationship existed between the cumulative penetration quantities and the time. There was no significant difference in the permeation quantities between the self-made and commercial cream. Conclusion The method is simple, rapid, and accurate, thereforeis a better method to evaluate the characteristic of permeation for triamcinolone acetonide acetate and econazole nitrate cream.%目的 建立醋酸曲安奈德益康唑乳膏体外透皮接收液中药物的HPLC测定方法,研究醋酸曲安奈德益康唑乳膏的体外透皮能力.方法 采用色谱柱:辛烷基硅烷键合硅胶为填充剂(5μm)(SP -120 -5 -C8 -AP)；流动相:以0.094％无水己烷磺酸钠[水-乙腈-异丙醇(720:40:40)]溶液(85％磷酸调pH =3)为流动相A,以0.094％己烷磺酸钠[水-甲醇( 100:900)]溶液(85％磷酸调pH =3)为流动相B,进行梯度洗脱；柱温为40℃；检测波长为227 nm;流速:1.0 mL/min;进样量为20μL.体外透皮实验采用改进的Franz立式扩散池,以实验用离体乳猪皮为透皮屏障,对比自制醋酸曲安奈德益康唑乳膏与市售乳膏的的透皮结果,分别在一定时间点取样测定透皮接收液中醋酸曲安奈德和硝酸益康唑的浓度,计算累积透皮量.结果 硝酸益康唑的回归方程为A=0.8834C+0.05075,相关系数r=0.9991,线性范围0.50 μg/mL -4.00 μg/mL,准确度均在85％ - 115％.累积透皮吸收量与时间呈良好的线性关系,自制乳膏与市售乳膏的透皮结果差异无显著性(P＞0.05).结论 该检测方法操作简便,快速准确,是考察醋酸曲安奈德益康唑乳膏体外透皮性能的较理想的方法.