Xi Ziyue, Zhang Wei, Fei Yali, Cui Mingshu, Xie Luyao, Chen Lu, Xu Lu
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Pharmaceutics. 2020 Feb 10;12(2):144. doi: 10.3390/pharmaceutics12020144.
This work explored absorption efficacy via an in vivo imaging system and parallel artificial membrane penetration in indomethacin (IMC) solid dispersion (SD) systems. Two different polymer excipients-hydroxypropyl methylcellulose (HPMC) and Kollicoat IR as precipitation inhibitors (PIs)-combined with mesoporous silica nanoparticles (MSNs) as carriers were investigated. The IMC-SDs were prepared using the solvent evaporation method and characterized by solubility analysis, infrared (IR) spectroscopy, powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FESEM), and differential scanning calorimetry (DSC). It was confirmed that IMC successfully changed into an amorphous state after loading into the designed carriers. The in vitro release and stability experiments were conducted to examine the in vitro dissolution rates of IMC-SDs combined with HPMC and Kollicoat IR as PIs which both improved approximately three-fold to that of the pure drug. Finally, in vivo studies and in vitro parallel artificial membrane penetration (PAMPA) experiments ensured the greater ability of enhancing the dissolution rates of pure IMC in the gastrointestinal tract by oral delivery. In brief, this study highlights the prominent role of HPMC and Kollicoat IR as PIs in MSN SD systems in improving the bioavailability and gastrointestinal oral absorption efficiency of indomethacin.
本研究通过体内成像系统以及吲哚美辛(IMC)固体分散体(SD)系统中的平行人工膜渗透来探究吸收效果。研究了两种不同的聚合物辅料——羟丙基甲基纤维素(HPMC)和作为沉淀抑制剂(PI)的尤特奇IR,它们与作为载体的介孔二氧化硅纳米颗粒(MSN)相结合。采用溶剂蒸发法制备了IMC-SD,并通过溶解度分析、红外(IR)光谱、粉末X射线衍射(PXRD)、场发射扫描电子显微镜(FESEM)和差示扫描量热法(DSC)对其进行表征。结果证实,IMC载入设计的载体后成功转变为无定形状态。进行了体外释放和稳定性实验,以考察与作为PI的HPMC和尤特奇IR相结合的IMC-SD的体外溶出速率,二者的溶出速率均比纯药物提高了约三倍。最后,体内研究和体外平行人工膜渗透(PAMPA)实验证实了通过口服给药增强纯IMC在胃肠道中溶出速率的更大能力。简而言之,本研究突出了HPMC和尤特奇IR作为PI在MSN SD系统中对提高吲哚美辛生物利用度和胃肠道口服吸收效率的显著作用。