青蒿琥酯干混悬剂的处方筛选及质量考察

Formula Optimization and Quality Observation of Artesunate Dry Suspension

目的:筛选青蒿琥酯干混悬剂的最佳处方,并对其质量进行考察。方法:以沉降体积比、再分散性以及干燥失重等为考察指标,分别采用单因素和正交试验考察填充剂、助悬剂、黏合剂和崩解剂的种类和用量,优选出最佳处方。采用HPLC法测定制剂中主药的含量,考察不同转速及溶出介质对其溶出行为的影响,并考察制剂在温度为(30±2)℃、相对湿度为(75±5)%条件下放置4个月的稳定性。结果:青蒿琥酯干混悬剂的最佳处方为:以蔗糖作为填充剂,15%微晶纤维素为崩解剂,8%黄原胶和12%羧甲基纤维素钠为助悬剂,浓度为6%的聚乙烯吡咯烷酮K30醇溶液(50%乙醇)为粘合剂。采用优化的处方制备4批样品,其标示含量均大于95%,沉降体积比均高于0.9,20 min时的溶出度均在80%以上,样品放置4个月后各项检测指标均符合要求,且无显著性变化。结论:所筛选的青蒿琥酯干混悬剂处方工艺简单、重复性好、稳定可控。

Objective： To optimize the formula of artesunate dry suspension,and evaluate the quality. Methods： With sedimentation volume ratio,redispersibility and loss on drying as the indices,single factor and orthogonal test were adopted to study the variety and amount of fillers,suspending agents,binders and disintegrating agents to optimize the formula. HPLC was used to determine the content of artesunate in the preparation. Different media and speed were used to investigate the dissolution behavior of artesunate dry suspension. The stability of the preparation was studied under the conditions of temperature（30 ± 2） ℃ and relative humidity（75 ±5） % for four months. Results： The optimal formula of artesunate dry suspension was as follows： sucrose as the filler,xanthan gum（8%） and CMC-Na（12%） as the suspending agent,MCC（15%） as the disintegrant and 6% PVP K30（in 50% ethanol solution）as the adhesive. Totally 4 batches of samples were prepared with the optimal formula,and their label contents were all above 95%,the sedimentation volume ratios were all higher than 0. 9 and the dissolution was more than 80% in 20 min. All the indices of samples met the requirements without significant change in 4 months. Conclusion： The preparation process of artesunate dry suspension is simple,reproducible and stable.