鲑降钙素吸入粉雾剂的制备及其药剂学性质研究

Preparation and pharmaceutical properties of salcatonin dry powder inhalations

目的 喷雾干燥法制备鲑降钙素吸入粉雾剂 ,考察其主要药剂学特性。方法 按中国药典 2 0 0 0年版方法测定鲑降钙素吸入粉雾剂排空率及有效部位沉积量 ,扫描电镜观察粉粒的形态 ,激光粒度测定仪测定粉粒的粒径大小及分布 ,差热分析及X射线粉末衍射考察吸入粉雾剂载体的晶型。结果 有效部位鲑降钙素沉积量均在 10 %以上 ,排空率均在 90 %以上 ;相对湿度在 5 2 %以下 ,粉粒呈圆整的分散状态 ;当RH =75 %时粉粒发生较多的粘连和聚集 ;粉体平均粒径为 1 6 7μm ;差热分析结果显示 :吸入粉雾剂中L 亮氨酸的熔融热较单一组分在喷雾干燥后显著下降 ;X射线粉末衍射图谱中 ,吸入粉雾剂载体的衍射峰强度较喷雾干燥前显著下降。结论 在鲑降钙素吸入粉雾剂载体系统中加入甘露醇 ,粉粒圆整 ,加入L 亮氨酸可形成超低密度载体 ;扫描电镜的结果提示 ,应严格控制吸入粉雾剂贮存时环境的湿度 ;

Aim To prepare salcatonin dry powder inhalations (sCT DPIs) A (mixture of mannitol and L leucine) and B (mixture of manntiol and lactose) by spray drying and then to study their main pharmaceutical properties. Methods Dumping rate of sCT DPIs capsules and deposited fraction of sCT at effective part were determined according to Chinese Pharmacopiea 2000. Particle morphology under different relative humidity (RH) was observed by scanning electronics microphotograph, particle size and its distribution were determined by Malvern Mastersizer and the transition of morphorous state for carriers before and after spray drying was investigated by differential thermal analysis (DTA) and X ray powder diffraction (XRPD). Results Dumping rates of sCT DPIs A and B capsules were both above 10% and deposited fraction of sCT at effective part was above 90% for both A and B, which were all in agreement with the standard of Chinese Pharmacopiea 2000. Powder particle of sCT DPIs A was round and existed one by one after keeping one month under RH 0, 23% and 52%, but aggregation can be observed under RH 75%; many particles which were also round agglomerated in sCT DPIs B even under zero RH; mean particle size of sCT DPIs A was 1 67 μm, which was much smaller than that of sCT DPIs B; In sCT DPIs A particle with empty core which was lighter than the same size particle with concreted core was observed. It was shown by DTA that melted heat of L leucine in sCT DPIs composed of mannitol and L leucine lowered much more than that of L leucine exisited alone after spray drying. It was confirmed by XRPD that diffraction intensity of carriers in sCT DPIs decreased more than that of carriers before spray drying. Conclusion Round particle can be made when mannitol was added to carriers and ultra low density carriers can be formed when L leucine was added. It was suggested by SEM that DPIs should be kept under certain RH. Particle size and distribution of sCT DPIs all accorded with demand of DPIs. Complex spray drying carriers formed amorphous state easier than single carrier.