吉非替尼片溶出度测定方法的考察

Study on Dissolution Method for Gefitinib Tablets

关键词:  吉非替尼  溶出度  方法学

Key words:  gefitinib  dissolution  methodology

摘要:

目的 建立吉非替尼片的溶出度试验方法。方法 应用桨法测定溶出度，并以HPLC测定样品中药物浓度，通过对溶出介质，转速和时间进行筛选，拟定吉非替尼片的溶出度试验方法，并以该方法测定不同制剂的溶出度。结果 采用桨法，转速50 r·min^-1，选取pH 1.0盐酸液、pH 4.5醋酸盐缓冲液、5%聚山梨酯80水溶液和含5%聚山梨酯80的pH 6.8磷酸盐缓冲液作为溶出介质，溶出截止时间为60 min。应用HPLC测定样品中药物浓度，溶出介质，辅料和滤膜吸附对测定无干扰，药物在10~300 μg·mL^-1内线性相关良好，回收率在98%~100%内，精密度及稳定性的RSD值均<2%。结论 建立的溶出度测定方法具有较强区分度，能为制剂处方工艺筛选提供评价依据。

Abstract:

OBJECTIVE To establish a dissolution method for gefitinib tablets. METHODS Paddle apparatus was used. The drug concentrations in samples were determined by HPLC. The dissolution media, rotational speed and time were investigated to establish the dissolution method. And dissolution test of different preparations were carried out by the established method. RESULTS The dissolution method was as follows: paddle apparatus, the rotational speed of 50 r·min^-1, and the dissolution time of 60 min. pH 1.0 hydrochloric acid solution, pH 4.5 acetate buffer solution, 5% Polysorbate 80 solution and pH 6.8 phosphate buffer solution containing 5% Polysorbate 80 were as dissolution media. Dissolution media, excipients and membrane adsorption did not interferer the determination of gefitinib in samples by HPLC. It showed good linearity in drug concentration from 10 μg·mL^-1 to 300 μg·mL^-1. The recoveries ranged from 98% to 100%. The RSD of precision and stability were less than 2%. CONCLUSION The dissolution method is discriminative, which is suitable as a standard method for the formulation study of gefitinib tablets.