化工进展

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反应结晶法制备琥珀酸舒马普坦干粉吸入剂及其评价

杨宗阳,胡婷婷,乐 园,刘 淼,沈志刚,陈建峰   

  1. 中新国际纳米技术工程研究中心,北京化工大学纳米材料先进制备技术与应用科学教育部重点实验室;北京化工大学教育部超重力工程研究中心
  • 出版日期:2008-09-05 发布日期:2008-09-05

Preparation of ultrafine sumatriptan succinate for dry powder inhalation via reactive crystallization

YANG Zongyang,HU Tingting,LE Yuan,LIU Miao,SHEN Zhigang,CHEN Jianfeng   

  1. Sin-China Nano Technology Center,Key Lab for Nanomaterials,Ministry of Education,Beijing University of Chemical Technology;Research Center for High Gravity Engineering Technology,Ministry of Education,Beijing University of Chemical Technology
  • Online:2008-09-05 Published:2008-09-05

摘要: 在四氢呋喃体系中以舒马普坦(碱)和丁二酸为反应物,采用反应结晶法制备琥珀酸舒马普坦干粉吸入剂。对影响产物粒径和形貌的因素,如反应物的配比、反应温度、搅拌速度等进行了考察,并对最优条件下所得的干粉进行了相关的物化性质表征。结果表明,当反应物的配比nST∶n丁二酸为1∶2、反应温度范围为0~15℃、搅拌速度为10000 r/min时,可以得到平均粒径大约为1 μm、且粒度分布窄的琥珀酸舒马普坦颗粒,其体外沉积实验结果明显优于现有市售琥珀酸舒马普坦产品,肺部沉积值大约提高了5倍。

Abstract: The purpose of this study was to produce ultrafine sumatriptan succinate (SS) for dry powder inhalation formulation via reactive crystallization. The effects of mole ratio of sumatriptan to succinic acid,reaction temperature and mixing intensity on particle size and morphology were investigated. Fourier transform infrared spectroscopy,scanning electron microscopy and X-ray diffraction were used to characterize the physicochemical properties of as-prepared SS dry powder. The results showed that ultrafine particles of SS with an average size of about 1μm could be produced and well controlled under the following conditions,mole ratio (nST∶nsuccinic acid) 1∶2,at 0—15 ℃,mixing intensity 10000r/min. Furthermore,after foundational aerosol performance evaluation,the fine particle fraction (FPF) (<5μm) was increased up to 25.35%,which was approximate 5 times of the FPF value for the milled commercial SS.

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