中南药学

目的 建立激光衍射法测定他达拉非原料药粒度和粒度分布，并进行方法学验证。方法采用Mastersizer 3000型激光粒度分析仪，湿法测定他达拉非的粒度与粒度分布。样品采用0.3%十二烷基硫酸钠（SDS）进行预分散，并用水为分散剂，遮光度在5%～20%，转速为2000 r/min，搅拌2 min。结果 研究成功建立了一种激光衍射法-湿法测定他达拉非原料药粒度分布的方法。通过系统优化，确定以0.3%十二烷基硫酸钠（SDS）溶液作为预分散剂，水为分散介质，遮光度控制在5%～20%，搅拌速度2000 r/min，分散时间2 min。在此条件下，他达拉非颗粒分散均匀，无聚集现象，Zeta电位稳定在-29 mV左右（RSD<10%），方法学验证结果良好。结论 本研究建立的方法在常规粒度测定方法验证基础上增加耐用性试验，使激光粒度测定方法的验证内容更科学和严谨，所建立的粒度测定方法简洁易行，可为易团聚难溶性原料药粒度测定方法的开发提供参考。

Objective To determine particle size and size distribution of tadalafil by laser diffraction. Methods The particle size and size distribution of tadalafil were measured by wet method with a Mastersizer 3000 laser particle size analyzer. The samples were pre-dispersed with 0.3% sodium dodecyl sulfate(SDS) and water as the dispersing agent with an obscuration rate of 5% to 20% at a stirring speed of 2000 r/min for 2 min. Results This study established a wet laser diffraction method for determining the particle size distribution of tadalafil API. Systematic optimization identified the optimal conditions as follows: 0.3% SDS as the pre-dispersant, water as the medium, with an obscuration of 5% ～ 20%, stirring at 2000 rpm for 2 min. Under these conditions, uniform dispersion without agglomeration was achieved, evidenced by a stable Zeta potential of approximately-29 mV(RSD < 10%). Method validation confirmed the reliability of the proposed method. Conclusion The laser scattering method for the determination of tadalafil particle size is established in this study, and the durability test is added besides conventional particle size determination, enabling more scientific verification of the laser particle size determination. The established method is simple and feasible, and provides reference for the development of particle size determination of easy agglomeration and insoluble bulk drugs.