介孔二氧化硅吲哚美辛固体分散体复合物的制备及质量评价

以吲哚美辛(IMC)为模型药物,选用聚乙烯吡咯烷酮k30(PVPk30)与介孔二氧化硅(SiO_2)Syloid SP53D作为共同载体材料,制备介孔二氧化硅固体分散体复合物,以提高固体分散体中主药的载药量和溶出度.采用溶剂蒸发法制备IMC-PVPk30固体分散体(简称IMC-PVPk30),浸没-溶剂蒸发法制备IMC-SiO_2固体分散体(简称IMC-SiO_2)和IMC-PVPk30-SiO_2固体分散体复合物(简称IMC-PVPk30-SiO_2);利用差示扫描量热法(DSC)、扫描电镜(SEM)等方法对其表征;采用紫外-可见分光光度法测定固体分散体及其复合物的载药量与溶出度. DSC显示,制备的两种固体分散体及其复合物中, IMC的熔点峰均消失,表明固体分散体制备成功; SEM显示, IMC-PVPk30结构呈不规则的块状,而IMC-SiO_2和IMC-PVPk30-SiO_2的粒径大小均匀,且IMC,PVPk30与介孔二氧化硅复合在一起;在不同pH的溶出介质中, IMC-SiO_2和IMC-PVPk30-SiO_2的溶出率均高于IMC-PVPk30,且IMC-PVPk30-SiO_2的溶出率最高.得出介孔二氧化硅吲哚美辛固体分散体复合物(IMC-PVPk30-SiO_2)具有较高的载药率和溶出率,为改善固体分散体的稳定性和进一步提高难溶性药物溶出度提出了新的思路和方法.

Preparation and Quality Evaluation of Mesoporous Silica Indomethacin Solid Dispersion Composite

Objective:To improve the drug loading efficiency, dissolution rate and stability of the main drug in the solid dispersion of mesoporous silica, polyvinylpyrrolidone k30 (PVPk30) and mesoporous SiO₂ Syloid SP53D were applied as solid dispersion carriers for indomethacin (IMC) to prepare the drug-loaded mesoporous SiO₂ solid dispersions (IMC-PVPk30-SiO₂). Methods:IMC-PVPk30 solid dispersion was prepared with the solvent evaporation method; IMC-SiO₂ solid dispersion and IMC-PVPk30-SiO₂ solid dispersion composite were prepared with the immersion-solvent evaporation method. Then samples were characterized by differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The drug loading efficiency and dissolution rate of the solid dispersion and its complex were determined by ultraviolet-visible spectrophotometry. Results:The results of DSC showed that the melting peak of IMC disappeared practically between IMC-PVPk30, IMC-SiO₂ and IMC-PVPk30-SiO₂, suggesting that IMC existed in the amorphous state in these samples and the solid dispersions were prepared successfully. SEM showed that the IMC-PVPk30 structure was irregularly blocked, and the IMC-SiO₂ and IMC-PVPk30-SiO₂ had a nearly identical particle size. Compared with the mesoporous SiO₂ materials, the particle size increased slightly, which indicated that IMC may be distributed on both the outer surface and the inner channel of SiO₂. The dissolution determination experiment showed that the dissolution rates of IMC-SiO₂ and IMC-PVPk30-SiO₂ were higher than those of IMC-PVPk30 within 2 hours. Conclusion:The IMC silica solid dispersion composite (IMC-PVPk30-SiO₂) has a high drug loading efficiency and dissolution rate, and it is expected to be a novel drug delivery system for poorly soluble drugs with better bioavailability.