激光衍射法测定地拉罗司的粒径分布及其与体外溶出度的相关性研究

• 作 者: 陈谕园 吴松 陈丽青 张媛媛 高钟镐 李天磊 黄伟 杨庆云
• 机 构: 中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室,北京100050
• 出 处: 中国药学（英文版）
• 发表日期: 2021年11期
• 关键词: Deferasirox Particle size distribution Laser diffraction Dissolution curve

地拉罗司是用于治疗成人和儿童地中海贫血患者铁超载的一线药物,属于BSC分类第Ⅱ类,在生产过程中应严格控制其原料药(API)的粒度及分布.本研究通过关键操作参数的摸索和优化,建立了一种准确、便捷的激光衍射法方法,应用于地拉罗司原料药粒径分布的测定.方法 学验证和实际样品测定的d(0.1)、d(0.5)、d(0.9)、d(4,3)值的相对标准偏均小于3％,表明该方法具有良好的精密度和准确度.采用不同粒径的地拉罗司原料药制备相应的分散片,并测定不同批次分散片在四种溶解介质中的溶出度曲线,考察粒径对药物体外溶出度的影响.结果 表明,地拉罗司原料药的粒径分布对其分散片的释放有显著影响.“,”Deferasirox is the first-line drug for iron overload due to thalassemia in adults and pediatric patients.It is classified as a type Ⅱ compound in the Biopharmaceutics Classification System,and thus the particle size of its active pharmaceutical ingredient (API)should be strictly controlled during the manufacturing process.In the present study,laser diffraction was adopted to measure the particle size distribution of deferasirox API.We also developed and validated an accurate and convenient method by investigating important optical parameters and sample dispersing conditions.The relative standard deviation values,namely,d (0.1),d (0.5),d (0.9),and d (4,3),measured via methodology validation and actual sample measurement were ＜ 3％.The dissolution curves of several batches of dispersible tablets prepared using deferasirox with different particle sizes were compared in the four dissolved media to investigate the influence of particle size on drug dissolution in vitro.Results indicated that the particle size distribution of deferasirox API significantly affected the release of its dispersible tablet.