管状介孔硅用于提高西洛他唑的溶出速率及对其物理稳定性的影响

Mesoporous silica tube for improvement of dissolution rate and physical stability of cilostazol

目的以合成不同于传统球形介孔硅的管状硅(mesoporous silica tube,MST)为载体,制备西洛他唑(cilostazol,CLT)固体分散体系(CLT-MST),提高难溶性药物CLT的溶出速率和物理稳定性。方法采用多壁纳米碳管(carbon nanotube,CNT)为硬模板,以表面活性剂十六烷基三甲基溴化铵(cetyltrimethyl ammonium bromide,CTAB)为辅助模板制备MST,应用扫描电子显微镜(scanning electron microscope,SEM)、透射电子显微镜(transmission electron microscope,TEM)和比表面积分析仪表征MST外在形貌和内部孔道特征。采用挥干载药的方法,将CLT载入制备的MST中,并测定所制备的固体分散体系的药物溶出度,以差示扫描量热仪(differential scanning calorimetry,DSC)和X射线衍射仪(X ray diffraction,XRD)分析药物在载体中的存在状态。最后对介孔硅固体分散体系进行稳定性试验。结果所制备CLT-MST在1 h时累计溶出度达到82%,且储存6个月后CLTMST的DSC和XRD表征图谱均没有显著变化。结论 MST可使难溶性药物CLT高度分散,能够改善CLT的溶出速率以及保持CLT的物理稳定性。

Objective Tube mesoporous silica cardersare synthesized, which are different from traditional silica carders. Aim to improve dissolution rate and physical stability of the insoluble drug, cilostazolis loaded into mesoporous silica carder （MST）. Methods CNT as hard template and CTAB as soft template were employed to prepare MST. Scanning electron microscopy （SEM）, transmission electron microscopy （TEM） and adsorption-desorption analysis were used to characterize MST as well. The solvent evaporation method was chosen to uptake drug into MST to prepare solid dispersion. Moreover the properties of the drug delivery system were studied by differential scanning calorimetry （DSC） and X-ray diffraction （XRD）. The dissolution of solid dispersion was measured by in vitro drug dissolution test and the long term stability research was also conducted. Results Tube silica carriers have been successfully prepared. Loading cilostazol solid dispersion could release 82% drug within 1 h. After 6 months, the stability of solid dispersion was maintained. Conclusions Dissolution rate of MST solid dispersion system is improved contributed to highly dispersion of drug particles and destroying structure of the crystalline. The physical stability is also kept because the rigid structure of silica carriers could inhibit aggregation of drug molecules.