熊莲洁, 朱家壁. 鲑降钙素吸入粉雾剂的制备及其药剂学性质研究鲑降钙素吸入粉雾剂的制备及其药剂学性质研究J. 药学学报, 2003, 38(3): 218-222.
引用本文: 熊莲洁, 朱家壁. 鲑降钙素吸入粉雾剂的制备及其药剂学性质研究鲑降钙素吸入粉雾剂的制备及其药剂学性质研究J. 药学学报, 2003, 38(3): 218-222.
XIONG Lian-jie, ZHU Jia-bi. Preparation and pharmaceutical properties of salcatonin dry powder inhalationsJ. Acta Pharmaceutica Sinica, 2003, 38(3): 218-222.
Citation: XIONG Lian-jie, ZHU Jia-bi. Preparation and pharmaceutical properties of salcatonin dry powder inhalationsJ. Acta Pharmaceutica Sinica, 2003, 38(3): 218-222.

鲑降钙素吸入粉雾剂的制备及其药剂学性质研究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

  • 摘要: 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2000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52%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1.67 μm;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;喷雾干燥复合载体更有助于无定形的形成。

     

    Abstract: AimTo 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. MethodsDumping 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). ResultsDumping 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. ConclusionRound 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.

     

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