目的 制备尼莫地平(NMP)/介孔二氧化硅纳米固体分散体，以期通过提高尼莫地平的溶出速率，改善尼莫地平的生物利用度。方法 采用软模板法分别制备2种介孔二氧化硅SBA-16和SBA-15，对其进行表征，采用熔融法和溶剂法分别制备尼莫地平/二氧化硅固体分散体，以氮吸附曲线，扫描电镜，X-射线衍射及差示扫描量热法对载药与载药体系进行表征，并对自制固体分散体的溶出速率与大鼠体内药动学进行研究。结果 SBA-16为规则的球形形貌，比表面积为775.8 m2·g-1，总孔体积为0.7 cm3·g-1。SBA-15为棒状结构，比表面积为449.1 m2·g-1，总孔体积为1.02 cm3·g-1;当载体与药物的投料比为3∶1以上时，药物以非晶型形式吸附于载体表面及载体孔道中;自制固体分散体给予大鼠ig后与进口市售制剂尼膜同相比，溶出度与生物利用度均有所提高。结论 介孔二氧化硅适用于尼莫地平纳米固体分散体的制备，所制纳米粒具有提高生物利用度的作用。
Abstract
OBJECTIVE To prepare solid dispersion of mesoporous silica- nimodipine (NMP) in hope of improving its dissolution rate and bioavailability. METHODS Two kinds of mesoporous silica, SBA-16 and SBA-15, were prepared by soft template method and characterized. Melting method and solvent method were carried out to prepare two kinds of NMP/mesoporous solid dispersions. Nitrogen sorption, SEM, X-ray and DSC were carried out to characterize the NMP/mesoporous solid dispersions. The tablets were prepared and the dissolution rate was determined. The bioavailability of NMP/mesoporous silica was evaluated in rats. RESULTS SBA-16 had regular spherical-like morphology. The specific surface area and total pore volume of SBA-16 were 775.8 m2·g-1and 0.7 cm3·g-1, respectively. And 2D hexagonal SBA-15 with the morphology of rod-like structure with long channels was successfully prepared and the specific surface area and total pore volume of SBA-15 were 449.1 m2·g-1 and 1.02 cm3·g-1, respectively. The drug in the carrier was in the form of microcrystal or amorphous when the drug/carrier ratio was above 3∶1. Compared with nimotop, the prepared tablets of mesoporous silica-nimodipine had an increased dissolution rate and an improved bioavailability. CONCLUSION The prepared mesoporous silica is suitable for the preparation of NMP/mesoporous solid dispersion which obtains an improved bioavailability.
关键词
介孔二氧化硅 /
尼莫地平 /
固体分散体 /
溶出速率 /
生物利用度
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Key words
mesoporous silica /
nimodipine /
solid dispersion /
dissolution rate /
bioavailability
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中图分类号：
R944
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参考文献
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脚注
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基金
国家重大科学研究计划(973计划)(2009CB930300)
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