氯雷他定纳米混悬剂冻干口崩片的制备与质量评价

Preparation and Quality Evaluation of Loratadine-loaded Nanosuspension Lyophilized Disintegrating Tablets

目的:制备氯雷他定纳米混悬剂冻干口崩片,评价其质量。方法:采用反溶剂沉淀-辅助超声技术法制备氯雷他定纳米混悬剂,并通过冷冻干燥工艺将其制备成口崩片,使用二因素三水平(32)析因设计优评估明胶浓度(X1)和甘露醇浓度(X2)对冻干口崩片的粒径大小(Y1)、崩解时限(Y2)、脆碎度(Y3)和5 min时药物溶出度(Y4)的影响,并得到氯雷他定纳米混悬剂冻干口崩片的最优处方组成;比较氯雷他定纳米混悬剂冻干口崩片在冻干前后的粒径分布,通过扫面电镜观察纳米混悬剂及其冻干口崩片的微观结构,对比氯雷他定纳米混悬剂冻干口崩片与氯雷他定口崩片的体外药物溶出速率。结果:经试验优化得到氯雷他定纳米混悬剂冻干口崩片的最佳处方为:明胶浓度为1.7%,甘露醇浓度为18.0%;冻干前后氯雷他定纳米混悬剂的粒径分布未发生显著变化;在扫面电镜下可以观察到氯雷他定纳米混悬剂呈不规则颗粒状分布,冻干口崩片呈多孔网状结构;制备的冻干口崩片与市售氯雷他定口崩片相比,崩解时限更短,药物溶出速度更快,在5 min内药物溶出度达到90%以上。结论:本研究将氯雷他定制备成纳米混悬剂冻干口崩片,处方设计合理,工艺可行,值得进一步研究。

Objective:To prepare loratadine-loaded nanosuspension lyophilized disintegrating tablets(LN-LDTs)and to evaluate the quality.Methods:The anti-solvent precipitation-assisted ultrasound method was used to prepare the loratadine nanosuspension(LN),and then it was prepared into disintegrating tablets by freeze-drying process.A 32 factorial design was applied to study the effects of independent variables at different concentrations of gelatin(X1)and mannitol(X2)on the dependent variables including the particle size distribution(Y1),disintegration time(Y2),friability(Y3)and drug dissolution(Y4).The particle size distribution of LN-LDTs was compared before and after lyophilization.The microstructure of LN and LN-LDTs were observed by scanning electron microscopy.The dissolution rates of LN-LDTs and loratadine disintegrating tablets(L-DTs)were compared in vitro.Results:The optimal formulation of LN-LDTs obtained through the experimental optimization was as follows:the gelatin concentration was 1.7%,and the mannitol concentration was 18.0%.The particle size distribution of LN did not change significantly before and after lyophilization.Under the scanning electron microscope,the particle size distribution of LN was irregular,and LN-LDTs had a porous network structure.Compared with L-DTs,LN-LDTs had shorter disintegration time with faster drug dissolution rate,and the dissolution rate reached above 90%within 5 minutes.Conclusion:Current study suggested that LN-LDTs have reasonable formulation design and feasible preparation process,which deserve further studies.