伊曲康唑颗粒溶出度测定及与生产工艺相关性探讨

Determination of Itraconazole Granules's Dissolution and Its Correlation with Production Process

目的:建立伊曲康唑颗粒溶出度测定方法,并探讨溶出曲线与生产工艺的相关性。方法:采用浆法和高效液相色谱法,以0.5%十二烷基硫酸钠的0.1 mol·L^(-1)盐酸溶液1000 mL为溶出介质,转速75 r·min^(-1),HPLC法测定,色谱柱:Agilent C18(250 mm×4.6 mm,5μm),流动相:甲醇-0.065 mol·L^(-1)醋酸铵-乙醚(70∶20∶6),流速:1.0 mL·min^(-1),柱温:35℃,检测波长:261 nm。结果:经方法学验证,伊曲康唑在0.02014~0.1208 mg·mL^(-1)的质量浓度范围内线性关系良好(r=0.9995),加样回收率为98.3%,精密度为0.6%。该方法可以对伊曲康唑颗粒的体外释放过程进行有效评价。结论:本法经方法学验证可用于伊曲康唑颗粒溶出度测定和工艺质量控制。

Objective： To establish a method for the determination of itraconazole granules＇ s dissolution and to discuss the correlation between dissolution curve and production process. Methods： Paddle and HPLC methods were applied. 0.5% sodium dodecyl sulfate in 0.1 mol·L^（-1） hydrochloric acid solution（1000 mL） was used as the dissolution medium and the rotation speed was kept at 75 r·min^（-1）. The analysis was carried out by using the method of HPLC. Chromatographic column was Agilent C18（250 mm×4.6 mm, 5μm） and methanol, 0.065 mol·L^（-1） ammonium acetate and ether（70∶20∶6） were used as mobile phase at the flow rate of 1.0 mL·min^（-1）. The temperature of column was 35℃ and the detection wavelength was at 261 nm. Results： It was verified by methodology that calibration cures were linear in the range of 0.02014-0.1208 mg·mL^（-1）（r=0.9995）, the average recovery rate was 98.3% and RSD was 0.6%. The method could be used to evaluate the release process of itraconazole granules in vitro. Conclusion： This method was validated by methodology and can be used for the determination of dissolution and the control of itraconazole granules＇ s process quality.